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Review

Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study

Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Science, Beijing Normal University, 19 XinjiekouWai Avenue, Beijing 100875, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 959; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020959
Submission received: 18 December 2020 / Revised: 11 January 2021 / Accepted: 12 January 2021 / Published: 19 January 2021
(This article belongs to the Section Biochemistry)

Abstract

:
Secondary metabolites isolated from plant endophytic fungi have been getting more and more attention. Some secondary metabolites exhibit high biological activities, hence, they have potential to be used for promising lead compounds in drug discovery. In this review, a total of 134 journal articles (from 2017 to 2019) were reviewed and the chemical structures of 449 new metabolites, including polyketides, terpenoids, steroids and so on, were summarized. Besides, various biological activities and structure-activity relationship of some compounds were aslo described.

1. Introduction

During the growth of microorganisms, some secondary metabolites biologically active are produced to make their lives better. Using chemical and biological methods, Elshafie et al. displayed that the cell-free culture filtrate of Burkholderia gladioli pv. agaricicola (Bga) Yabuuchi has a promising antibacterial activity against the two microorganisms B. megaterium and E. coli [1]. Camele et al. reported that the tested isolate of an endophytic bacterium Bacillus mojavensis showed antagonistic bacterial and fungal activities against several strains as well as biofilm formation ability [2]. Endophytes refer to the microorganisms that exist in various organs, tissues or intercellular space of plants, while the host plants generally do not show any symptoms of infection. Generally speaking, endophytes include endophytic fungi, endophytic bacterium and endophytic actinomycetes [3]. As a very important microbial resource, endophytes exist widely in nature. It is ubiquitous in various terrestrial and aquatic plants. Endophytes have been isolated from bryophytes, ferns, pteridophytes, hornworts, herbaceous plants and various woody plants. The region also ranges from tropical to arctic, from natural wild to agricultural industry ecosystem [4]. They have unique physiological and metabolic mechanisms, which enable them to adapt to the special environment inside plants, and at the same time, they can encode a variety of bioactive substances. In addition, endophytes coevolved with the host plants for a long time to produce some metabolic substances similar or identical to the host plants with medicinal value [5]. Some endophytes can even assist the host of medicinal plants to synthesize effective active compounds, the ground-breaking discovery provides a new method to produce the effective compounds which have similar effects with natural medicines isolated from plant tissues directly. At the same time, it has solved the problem of resource shortage and ecological destruction caused by slow growth of some natural plants and large amount of artificial exploitation [3]. The more beneficial thing is that some of them are environmentally friendly. Elshafie et al. have studied the fungus Trichoderma harzianum strain T22 (Th-T22) and indicated that Th-T22 showed significant mycoremediation ability in diesel-contaminated sand, suggesting that it can be used as a bioremediation agent for diesel spills in polluted sites [6]. Among the common endophytes, the endophytic fungi are most often isolated [4]. The first endophytic fungus was isolated from Perennial ryegrass (Loliumtum eletum) seeds by Vogle in 1898 [7]. Up to now, the study on endophytic fungi has a long history of more than 100 years, but the research on endophytic fungi of medicinal plants has not been formally carried out until the last 30 years, which has gradually attracted the attention of domestic and foreign scholars.
The multiformity of endophytes enable they can produce a variety of secondary metabolites. In recent years, the metabolites isolated from the endophytic fungi include alkaloids, steroids, terpenes, anthraquinones, cyclic peptides, flavonoids commonly [5]. Some secondary metabolites exhibit high biological activities. The antitumor, antibacterial, anti-inflammatory, antiviral, antifungal and other compounds have been produced by different endophytic fungi. Therefore, the chemical variety of secondary metabolites produced by endophytic fungi has advantage for new drug development [8].
In this review, 449 new secondary metabolites, together with their chemical structures and biological activities were summarized. The structure-activity relationships and absolute configureuration of some compounds have also been described. Among all new compounds, terpenoids account for the largest proportion (75%), followed by polyketones (36%). The proportion of different types of compounds in all new compounds is shown in Figure 1. These new compounds were isolated from various fungi associated with different tissues from different plants. As a result, their structures varied a lot, which leads to their multitudinous biological activities. In addition to common antimicrobial activity and anti-tumor activity, some compounds also showed anti-enzyme activity and inhibition of biofilm formation, inhibition of phytoplankton growth, and so on.

2. New Metabolites Isolated from Plant Endophytes

2.1. Terpenoids

2.1.1. Sesquiterpenoids and Their Derivatives

Five new polyketide-terpene hybrid metabolites 15 (Figure 2) with highly functionalized groups, were isolated from the endolichenic fungus Pestalotiopsis sp. [9]. Co-cultivation of mangrove endophytic fungus Trichoderma sp. 307 and aquatic pathogenic bacterium Acinetobacter johnsonii B2 led to the production of two new furan-type isoeremophilane sesquiterpenes, microsphaeropsisin B 6 and microsphaeropsisin C 7 (Figure 2). Their absolute configureuration were assigned as 4S, 5R, 7R, 8S, 11S and 4R, 5R, 7R, 8S [10]. Following cultivation on rice medium, a new sesquiterpene, atrichodermone C 8 (Figure 2), was isolated from an endophytic fungal strain named Trichoderma atroviride which was isolated from the bulb of Lycoris radiate [11]. There is an endophytic fungus Pestalotiopsis sp. which was obtained from fruits of Drepanocarpus lunatus (Fabaceae). Co-culture of this fungus with Bacillus subtilis afforded two new sesquiterpenoids pestabacillins A 9 (Figure 2) and pestabacillins B 10 (Figure 2) [12]. Two new sesquiterpene-epoxycyclohexenone conjugates, nectrianolins A 11 (Figure 2) and nectrianolins B 12 (Figure 2), together with a sesquiterpene, nectrianolin C 13 (Figure 2), were isolated from the brown rice culture of Nectria pseudotrichia 120-1NP, an endophytic fungus isolated from Gliricidia sepium. It is of particular interest that 11 and 12 have a rearranged monocyclofarnesyl skeleton (which is uncommon to sesquiterpene-epoxycyclohexane conjugates) instead of a bicyclofarnesyl skeleton which is present in macrophorins, neomacrophorins, myrothecols, and craterellins [13]. It was found that endophytic Nigrospora oryzae stimulated the production of a new tremulane sesquiterpene nigrosirpexin A 14 (Figure 2) from Irpex lacteus [14]. Two novel sesquiterpenoids with an unprecedented tricyclo[4,4,2,1]hendecane scaffold, namely emericellins A 15 (Figure 2) and emericellins B 16 (Figure 2) representing a new skeleton, were isolated from the liquid cultures of an endophytic fungus Emericella sp. XL 029 associated with the leaves of Panax notoginseng [15]. Two trichothecene sesquiterpenoids, trichothecrotocins A 17 (Figure 2) and trichothecrotocins B 18 (Figure 2), and a pair of merosesquiterpenoid racemates, (+)-trichothecrotocin C 19 (Figure 2) and (−)-trichothecrotocin C 20 (Figure 2), were obtained from potato endophytic fungus Trichothecium crotocinigenum by bioguided isolation. Compounds 17 and 18 are trichothecenes possessing new ring systems. Compounds 19 and 20 possess novel 6/6−5/5/5 fused ring system [16]. Chemical investigation on the solid rice culture of Trichoderma atroviride S361, an endophyte isolated from Cephalotaxus fortunei, has afforded a new cyclohexenone sesquiterpenoid, trichodermadione B 21 (Figure 2) [17]. Seven new phenolic bisabolane sesquiterpenoids, (7R,10S)-7,10-epoxysydonic acid 22 (Figure 2), (7S,10S)-7,10-epoxysydonic acid 23 (Figure 2), (7R,11S)-7,12-epoxysydonic acid 24 (Figure 2), (7S,11S)-7,12-epoxysydonic acid 25 (Figure 2), 7-deoxy-7,14-didehydro-12-hydroxysydonic acid 26 (Figure 2), (Z)-7-deoxy-7,8-didehydro-12-hydroxysydonic acid 27 (Figure 2), and (E)-7-deoxy-7,8-didehydro-12-hydroxysydonic acid 28 (Figure 2), were obtained from the culture of an endophytic fungus Aspergillus sp. xy02 isolated from the leaves of a Thai mangrove Xylocarpus moluccensis [18]. Pestalustaines A 29 (Figure 2), one unique sesquiterpene possessing an unusual 5/6/7-fused tricyclic ring system was isolated from the plant-derived Pestalotiopsis adusta [19]. A new acorane sesquiterpene, 3β-hydroxy-β-acorenol 30 (Figure 2), possesses an acorane framework was separated from the extract of the green Chinese onion derived fungus Fusarium proliferatum AF-04 [20]. An examination of the endophytic fungus Trichoderma asperellum A-YMD-9-2 obtained from the marine red alga Gracilaria verrucosa led to the isolation of seven new chromanoid norbisabolane derivatives, trichobisabolins I–L 3134 (Figure 2) and trichaspsides C–E 3537 (Figure 2). The discovery of compounds 3137 greatly diversifies the structures of norbisabolane sesquiterpenes [21]. Oxytropiols A–J 3847 (Figure 2), ten undescribed highly oxygenated guaiane-type sesquiterpenoids, were isolated from the locoweed endophytic fungus Alternaria oxytropis [22]. Studies on the bioactive extract of mangrove endophytic fungus Pleosporales sp. SK7 led to the isolation of an abscisic acid-type sesquiterpene 48 (Figure 2), named (10S, 2Z)-3-methyl-5-(2,6,6-trimethyl-4-oxocyclohex-2-enyl)pent-2-enoicacid [23]. One new tremulane sesquiterpene, irpexlacte A 49 (Figure 2), was isolated from the endophytic fungus Irpex lacteus DR10-1 waterlogging tolerant plant Distylium chinense [24]. Trichocadinins B−G 5055 (Figure 2), six new cadinane-type sesquiterpene derivatives, each with C-14 carboxyl functionality, were isolated from the culture extract of Trichoderma virens QA-8, an endophytic fungus obtained from the fresh inner tissue of the medicinal plant Artemisia argyi [25]. Chemical investigation of the EtOAc extract of the plant-associated fungus Alternaria alternate in rice culture led to the isolation of a new sesquiterpene (1R,5R,6R,7R,10S)-1,6-Dihroxyeudesm-4(15)-ene 56 (Figure 2) [26]. An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation of five protoilludane-type sesquiterpenes named epicoterpenes A–E 5761 (Figure 2). Compound 60 was the first example of an ent-protoilludane sesquiterpenoid scaffold bearing a five-membered lactone. Notably, none of the new compounds were produced by either of the two fungi when cultured alone under the same conditions [27]. A new sesquiterpene lactone, namely colletotrin 62 (Figure 2), was obtained from a rice culture of Colletotrichum gloeosporioides, an endophytic fungus isolated from the stem bark of Cameroonian medicinal plant Trichilia monadelpha (Meliaceae) [28]. Purpurolide A 63 (Figure 2), an unprecedent sesquiterpene lactone with a rarely encountered 5/5/5 spirocyclic skeleton, along with two new 6/4/5/5 tetracyclic sesquiterpene lactones purpurolide B and C 6465 (Figure 2), were isolated from the cultures of the endophytic fungus Penicillium purpurogenum IMM003 [29]. Bioassay-guided fractionation of the crude extract of fermentation broth of one symbiotic strain Fusarium oxysporum ZZP-R1 derived from coastal plant Rumex madaio Makino, one traditional Chinese medicine used as a treatment of inflammation and toxication, yielded one novel compound, fusariumins D 66 (Figure 2). Chemical structure of 66 was determined as a sesquiterpene ester with a conjugated triene and an unusual oxetene ring by a combination of spectroscopic methods [30].

2.1.2. Diterpenoids

One new cleistanthane-type diterpene zythiostromic acid C 67 (Figure 3), which structure was assigned as 3α,5α,7β,8β-tetrahydroxycleistanth-13(17),15-dien-18-oic acid, was isolated from the brown rice culture of Nectria pseudotrichia 120-1NP [31]. A fungal strain, Drechmeria sp., was isolated from the root of Panax notoginseng. Totally, seven new indole diterpenoids, drechmerins A–G 6874 (Figure 3), were isolated from the fermentation broth of Drechmeria sp. [32]. A novel 1(2), 2(18)-diseco indole diterpenoid, drechmerin H 75 (Figure 3), was isolated from the fermentation broth of Drechmeria sp. together with a new indole diterpenoid, 2′-epi terpendole A 76 (Figure 3) [33]. An endophytic fungus, Neosartorya fifischeri JS0553, was isolated from G. littoralis plant. From the fungus, a new meroditerpenoid named sartorypyrone E 77 (Figure 3) was isolated [34]. Two new oxoindolo diterpene epimers, anthcolorin G 78 (Figure 3) and anthcolorin H 79 (Figure 3), isolated for the first time from a natural source, were isolated from the solid rice culture of the endophytic fungus Aspergillus versicolor [35]. A new isopimarane derivative which was named as xylaroisopimaranin A 80 (Figure 3) and the absolute configureurations was determined as 4S, 5R, 9R, 10R, 13R and 14S, was isolated from the plant endophytic fungus Xylaralyce sp. (HM-1) [36]. The endolichenic fungus Apiospora montagnei isolated from the lichen Cladonia sp. was cultured on solid rice medium, yielding a new diterpenoid libertellenone L 81 (Figure 3), compound 81 represented the first example of 6,7-seco-libertellenone derivative [37].

2.1.3. Other Terpenoids

Eleven new ophiobolin-type sesterterpenoids, asperophiobolins A−K 8292 (Figure 4), were isolated from the cultures of the mangrove endophytic fungus Aspergillus sp. ZJ-68. Asperophiobolins A–D (8285) represented the first examples possessing a five-membered lactam unit between C-5 and C-21 in ophiobolin derivatives. The absolute configureuration of compands were defined as (2S,3R,5S,6R,11R,14R,15S) (8284), (2S,3R,5S,6R,10S,11R,14R,15S) (85), (2S,6S,10S,11R,14R,15S,18R) (87), (2S,6R,10S,11R,14R,15S,18R) (88), (2S,6S,10S,11R,14R,15S,18S) (89), (2S,6R,10S,11R,14R,15S,18S) (90),(2S,3R,6R,10S,11R,14R,15S,18S) (91), (2R,3R,5R,6R,10S,11R,14R,15S) (92) [38]. From Kadsura angustifolia fermented by an associated symbiotic endophytic fungus, Penicillium sp. SWUKD4.1850, nine undescribed triterpenoids, kadhenrischinins A–H 93100 (Figure 4), and 7β-schinalactone C 101 (Figure 4) were isolated and established. All these metabolites have been first detected in non-fermented K. angustifolia. Structurally, kadhenrischinins A–D (9396) belong to the relatively rare class of highly oxygenated schitriterpenoids that contain a unique 3-one-2-oxabicyclo [3,2,1]-octane motif, while kadhenrischinins E–H (97100) feature acyclopentane ring in a side chain rarely found in the family Schisandraceae [39]. Meroterpenoids with diverse ring systems including five new ones (102106) (Figure 4), were isolated from Phyllosticta capitalensis, an endophytic fungus from Cephalotaxus fortunei Hook. Compound 102 was the first example with a 9,14-seco ring and a five-membered ring in guignardone derivatives. Compound 103 represented a novel guignardone derivative possessing a 5/7/6/5 ring system with CH2-7 attached to C-4 rather than C-6 in ring D [40]. Nine new meroterpenes, (7R,8R)-8-hydroxysydowic acid 107 (Figure 4), (7S,10S)-10-hydroxy-sydowic acid 108 (Figure 4), (7S,11R)-12-hydroxy-sydowic acid 109 (Figure 4), (7S,11R)-12-acetoxy-sydowic acid 110 (Figure 4), (7R,8R)-1,8-epoxy-11-hydroxy-sydonic acid 111 (Figure 4), 7-deoxy-7,14-didehydro-11-hydroxysydonic acid 112 (Figure 4), 7-deoxy-7,14-didehydro-12-acetoxy-sydonic acid 113 (Figure 4), and (E)-7-deoxy-7,8-didehydro-12-acetoxy-sydonic acid 114 (Figure 4), (7R)-11-hydroxy-sydonic acid methyl ester 115 (Figure 4), were isolated from the solid rice culture of the endophytic fungus Aspergillus versicolor [35]. Bioassay-guided fractionation of the crude extract of fermentation broth of one symbiotic strain Fusarium oxysporum ZZP-R1 derived from coastal plant Rumex madaio Makino, one traditional Chinese medicine used as a treatment of inflammation and toxication, yielded one novel compound, fusariumins C 116 (Figure 4). Chemical structure of 116 was determined as one meroterpene with cyclohexanone moiety [30]. A new monoterpentoid lithocarin D 117, was isolated from the endophytic fungus Diaporthe lithocarpus A740 (Figure 4) [41].

2.2. Ketone Compounds

2.2.1. Polyketides

An endophytic fungus, Eupenicillium sp. LG41, isolated from the Chinese medicinal plant Xanthium sibiricum, was subjected to epigenetic modulation using an NAD+-dependent histone deacetylase (HDAC) inhibitor, nicotinamide. Epigenetic stimulation of the endophyte led to enhanced production of two new decalin-derived polyketides with a double bond between C-3 and C-4, eupenicinicols C 118 (Figure 5) and D 119 (Figure 5) [42]. On the basis of One Strain/Many Compounds (OSMAC) strategy, five new polyketides, named phomopsiketones A–C 120122 (Figure 5), (10S)-10-O-b-D-40-methoxymannopyranosyldiaporthin 123 (Figure 5), and clearanol 124 (Figure 5), were isolated from an endophytic fungus, Phomopsis sp. sh917, harbored in stems of Isodon eriocalyx var. laxiflora [43]. As naturally occurring polyketides, ten new salicyloid derivatives, namely vaccinols J–S 125134 (Figure 5), were isolated from Pestalotiopsis vaccinii (cgmcc3.9199) endogenous with the mangrove plant Kandelia candel (L.) Druce (Rhizophoraceae) [44]. Twelve new polyketides, penicichrysogenins A–L 135146 (Figure 5), were isolated from the solid substrate fermentation cultures of a Huperzia serrata endophytic fungus Penicillium chrysogenum MT-12. The structures of 135139 were established as (2R)-6-hydroxy-2,4-dimethoxy-5-methylphthalide (135), 4,6-dihydroxy-5-hydroxymethylphthalide9 (136), 4,6-dihydroxy-5-methoxymethylphthalide (137), (2R)-4,5-dihydroxy-2,6-dimethoxy-2-pentylphthalide (138), (E)-4,5-dihydroxy-2-(4-hydroxypentylidene)-6-methoxyphthalide(139), respectively [45]. Three new polyketides, cylindrocarpones A–C 147149 (Figure 5), were isolated from the endophytic fungus, Cylindrocarpon sp., obtained from the tropical plant Sapium ellipticum [46]. Six new xanthone-derived polyketides, named phomoxanthones F–K 150155 (Figure 5), were isolated from Phomopsis sp. xy21, which was isolated as an endophytic fungus from the Thai mangrove Xylocarpus granatum. Phomoxanthone F 150 represented the first xanthone-derived polyketide containing a 10a-decarboxylated benzopyranone nucleus that was substituted by a 4-methyldihydrofuran-2(3H)-one moiety at C10a. Phomoxanthones G 151 and H 152 are highly oxidized xanthone-derived polyketides containing a novel 5-methyl-6-oxabicyclo [3.2.1] octane motif [47]. Compound 156 (Figure 5), 5,9-dihydroxy-2,4,6,8,10-pentamethyldodeca-2,6,10-trienal, a novel polyketide molecule was isolated from Aspergillus flocculus endophyte isolated from the stem of the medicinal plant Markhamia platycalyx [48]. Three new polyketides, (2S)-2,3-dihydro-5,6-dihydroxy-2-methyl-4H-1-benzopyran-4-one 157 (Figure 5), (2′R)-2-(2′-hydroxypropyl)-4-methoxyl-1,3-benzenediol 158 (Figure 5), and 4-ethyl-3-hydroxy-6-propenyl-2H-pyran-2-one 159 (Figure 5) were isolated from the culture broth of Colletotrichum gloeosporioides, an endophytic fungus derived from the mangrove Ceriops tagal [49]. Five polyketides, paralactonic acids A–E 160164 (Figure 5) were isolated from Paraconiothyrium sp. SW-B-1, an endophytic fungus isolated from the seaweed, Chondrus ocellatus Holmes [50]. Four new polyketides, alternatains A–D 165168 (Figure 5), were obtained from the solid substrate fermentation cultures of Alternaria alternata MT-47, an endophytic fungus isolated from the medicinal plant of Huperzia serrata [51]. From extracts of the plant associated fungus Chaetosphaeronema achilleae collected in Iran, two polyketides including a previously unreported isoindolinone named chaetosisoindolinone 169 (Figure 5) and a previously undescribed indanone named chaetosindanone 170 (Figure 5) were isolated [52]. During a survey of the secondary metabolites of endophytic fungi Aspergillus porosus, new polyketides with interesting structural features named porosuphenols A–D 171174 (Figure 5) were found [53]. Chemical investigation of the EtOAc extract of the plant-associated fungus Alternaria alternate in rice culture led to the isolation of a novel liphatic polyketone, alternin A 175 (Figure 5), which possesses an unprecedented C25 liphatic polyketone skeleton [26]. Five new polyketides, colletotric B 176 (Figure 5), 3-hydroxy-5-methoxy-2,4,6-trimethylbenzoic acid 177 (Figure 5), colletotric C 178 (Figure 5), chaetochromone D 179 (Figure 5) and 8-hydroxy-pregaliellalactone B 180 (Figure 5), were isolated from thmangrove endophytic fungus Phoma sp. SYSU-SK-7 [54]. The EtOAc extract of Phomopsis sp. D15a2a isolated from the plant Alternanthera bettzickiana following fermentation on solid rice medium yielded three new polyketides, phomopones A−C 181183 (Figure 5) [55]. Three new polyketides including two benzophenone derivatives, penibenzones A (184) and B (185) (Figure 5), and a new phthalide derivative, penibenzone C 186 (Figure 5), were isolated from the solid-substrate cultures of the endophytic fungus Penicillium purpurogenum IMM003 [56].

2.2.2. Other Ketones

A new N-methoxypyridone analog 11S-hydroxy-14-methyl cordypyridone C 187 (Figure 6), was isolated from the co-culture of Hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062 [57]. A novel endophyte Rhytismataceae sp. DAOMC 251461 produced two new dihydropyrones: (R)-4-hydroxy-5-octanoyl-6-oxo-3,6-dihydropyran-2-carboxylic acid (rhytismatone A) 188 (Figure 6) and (R)-methyl-4-hydroxy-5-octanoyl-6-oxo-3,6-dihydropyran-2-carboxylate (rhytismatone B) 189 (Figure 6) [58]. Five new bioactive 2-pyrone metabolites, phomaspyrones A–E 190194 (Figure 6), were isolated from the culture broth of an endophytic fungus Phomopsis asparagi SWUKJ5.2020 of medicinal plant Kadsura angustifolia. The structures of 190194 were identified as (S)-5-(1,2-dihydroxyethyl)-6-hydroxymethyl-4-methoxy-2H-pyran-2-one (190),(S)-5-(1-hydroxyethyl)-6-hydroxymethyl-4-methoxy-2H-pyran-2-one (191), (5S,8R)-5,8-dihydroxy-4-methoxy-5,6-dihydropyrano-[3,4-b]pyran-2(8H)-one (192), 4-methoxy-6-methyl-5-(2-oxobutyl)-2H-pyran-2-one (193), 6-(hydroxymethyl)-4-methoxy-5-(2-oxobutyl)-2H-pyran-2-one (194) respectively [59]. Extracts from an endophytic fungus Dendrothyrium variisporum isolated from the roots of the Algerian plant Globularia alypum produced two new minor furanone derivatives: methyl (5S)-5-[(10E,30Z)-hexa-1,3-dienyl]-5-methyl-4-oxo-2-methyl-4,5-dihydrofuran-3 carboxylate ((5S) cis-gregatin B) 195 (Figure 6), (5R)-5-[(10E,30Z)-hexa-1,3-dienyl]-5-methyl-4-oxo-2-[(4S,1E)-4-hydroxypent-1-enyl]-4,5-dihydrofuran-3carboxylate, (graminin D) 196 (Figure 6) [60]. Two new compounds isobenzofuranone A 197 (Figure 6) and indandione B 198 (Figure 6), were isolated from liquid cultures of an endophytic fungus Alternaria sp., which was obtained from the medicinal plant Morinda officinalis. Among them, the indandione 198 showed a rarely occurring indanone skeleton in natural products [61]. An endophytic fungal strain named Trichoderma atroviride was isolated from the bulb of Lycoris radiata. Following cultivation on rice medium, a new cyclopentenone derivative, atrichodermone B 199 (Figure 6), was isolated [11]. One previously undescribed isochromone derivative 6,8-dihydroxy-3-(2-hydroxypropyl)-7-methyl-1H-isochromen-1-one 200 (Figure 6), was isolated from the culture of the endophytic fungus Eurotium chevalieri KUFA 0006 [62]. One previously undescribed pyrone (simplicilopyrone) 201 (Figure 6) was isolated from the endophytic fungus Simplicillium sp. PSU-H41 [63]. Cytosporaphenones A–C, one new polyhydric benzophenone 202 (Figure 6) and two new naphtopyrone derivatives 203204 (Figure 6), were isolated from Cytospora rhizophorae, an endophytic fungus from Morinda officinalis [64]. A novel pyrone derivative 205 (Figure 6) bearing two fused five-member rings, together with two new naphthalenone derivatives 206207 (Figure 6), were obtained from the endophytic fungus Fusarium sp. HP-2, which was isolated from “Qi-Nan” agarwood [65]. Two new compounds penibenzophenones A-B 208209 (Figure 6), were isolated from the EtOAc extract of the endophytic fungus Penicillium citrinum HL-5126 isolated from the mangrove Bruguiera sexangula var. rhynchopetala collected in the South China Sea [66]. Two new isochromanone derivatives, (3S,4S)-3,8-dihydroxy-6-methoxy-3,4,5-trimethylisochroman-1-one 210 (Figure 6) and methyl (S)-8-hydroxy-6-methoxy-5-methyl-4a-(3-oxobutan-2-yl)benzoate 211 (Figure 6), were isolated from the cultures of an endophytic fungus Phoma sp. PF2 obtained from Artemisia princeps [67]. Isoshamixanthone 212 (Figure 6), a new stereoisomeric pyrano xanthone was obtained from the endophytic fungal strain Aspergillus sp. ASCLA isolated from leaf tissues of the medicinal plant Callistemon subulatus [68]. From the endophytic fungus, Cylindrocarpon sp., obtained from the tropical plant Sapium ellipticum, a new pyrone cylindropyrone 213 (Figure 6) was isolated [46]. One new benzophenone derivative, named tenllone I 214 (Figure 6), was isolated from the endophytic fungus Diaporthe lithocarpus A740 [41].

2.3. Alkaloids and Their Derivatives

The endolichenic fungus Apiospora montagnei isolated from the lichen Cladonia sp. was cultured on solid rice medium, yielding a new pyridine alkaloid, 23-O-acetyl-N-hydroxyapiosporamide 215 (Figure 7) [37]. Chaetoindolin A 216 (Figure 7), a new indole alkaloid derivative was isolated from the endophytic fungus Chaetomium globosum CDW7 [69]. A synthetic α,β-unsaturated amide alkaloid (E)-tert-butyl(3-cinnamamidopropyl) carbamate 217 (Figure 7), newly identified as a natural product, was isolated from the EtOAc extract of the endophytic fungus Penicillium citrinum HL-5126 isolated from the mangrove Bruguiera sexangula var. Rhynchopetala [66]. A new alkaloid, 1, 2-dihydrophenopyrrozin 218 (Figure 7), was isolated from an axenic culture of the endophytic fungus, Bionectria sp., obtained from seeds of the tropical plant Raphia taedigera [70]. Two new pyridone alkaloids, cylindrocarpyridones A–B 219220 (Figure 7), were isolated from the endophytic fungus, Cylindrocarpon sp., obtained from the tropical plant Sapium ellipticum [46]. From Aspergillus versicolor, an endophyte derived from leaves of the Egyptian water hyacinth Eichhornia crassipes (Pontederiaceae), one new compound aflaquinolone H 221 (Figure 7) belonging to dihydroquinolone alkaoids was obtained [71]. Two new spiroketal derivatives as alkaloids with an unprecedented amino group, 2′-aminodechloromaldoxin 222 (Figure 7) and 2′-aminodechlorogeodoxin 223 (Figure 7), were isolated from the plant endophytic fungus Pestalotiopsis flavidula [72]. The biotransformation of lycopodium alkaloid huperzine A (hupA), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. Two previously undescribed compounds 224225 (Figure 7), were isolated and identified [73]. Chemical investigation of the EtOAc extract of the plant-associated fungus Alternaria alternate in rice culture led to the isolation of a new indole alkaloid 226 (Figure 7) [26]. Bioactivity-guided isolation of the endophytic fungus Fusarium sambucinum TE-6L residing in Nicotiana tabacum L. led to the discovery of two new angularly prenylated indole alkaloids (PIAs) with pyrano[2,3-g]indole moieties, amoenamide C 227 (Figure 7) and sclerotiamide B 228 (Figure 7). Compound 227 containing the 8 bicyclo[2.2.2]diazaoctane core and indoxyl unit was rarely reported [74].

2.4. Penylpropanoids and Their Derivatives

A new isocoumarin (3R,4S,4aR,6R)-4,6,8-trihydroxy-3-methyl-3,4,4a,5,6,7-hexahydroisochromen-1-one 229 (Figure 8) was isolated from an endophyte Mycosphaerellaceae sp. DAOMC 250863 [58]. Using the bioassay-guided method, one new isocoumarin derivative, prochaetoviridin A 230 (Figure 8), was isolated from C. globosum CDW7, an endophyte from Ginkgo biloba [66]. A new isocoumarin derivative pestalotiopisorin B 231 (Figure 8), was isolated from Pestalotiopsis sp. HHL-101, an endophytic fungus obtained from Chinese mangrove plant Rhizophora stylosa [75]. In continuing search of fungal strain Nectria pseudotrichia 120-1NP, two new isocoumarins, namely, nectriapyrones A 232 (Figure 8) and B 233 (Figure 8) were identified [31]. Two new isocoumarin dimers 234235 (Figure 8) were isolated from Aspergillus versicolor, an endophyte derived from leaves of the Egyptian water hyacinth Eichhornia crassipes (Pontederiaceae) [71]. Pestalustaines 236 (Figure 8), one unprecedented coumarin derivative bearing 6/6/5/5-fused tetracyclic ring system, was isolated from a plant-derived endophytic fungus Pestalotiopsis adusta [19]. Compounds 237 (Figure 8) and 238 (Figure 8), determined as two novel isocoumarin derivatives with a different butanetriol group at C-3, were produced by T. harzianum (Trichoderma harzianum) Fes1712 isolated from Rubber Tree Ficus elastica leaves [76]. Two pairs of new isocoumarin derivatives penicoffrazins B and C, 239240 (Figure 8), were isolated from Penicillium coffeae MA-314, an endophytic fungus obtained from the fresh inner tissue of the leaf of marine mangrove plant Laguncularia racemosa [77]. A new dihydroisocoumarin, diaporone A 241 (Figure 8), was isolated from the ethyl acetate extract of the cultures of the endophytic fungus Diaporthe sp. [78].

2.5. Lactones

From the seeds of the traditional medicinal plant Ziziphus jujuba growing in Uzbekistan, the fungal endophyte Alternaria sp. was isolated. Extracts of this fungus yielded a new natural phthalide derivative 7-methoxyphthalide-3-acetic acid 242 (Figure 9) [79]. Three new lactone Derivatives isoaigialones, A, B, and C 243245 (Figure 9), were isolated from the crude EtOAc extract of a Phaeoacremonium sp., an endophytic fungus obtained from the leaves of Senna spectabilis. 245 is epimeric at C-7 relative to compound 244 [80]. A new phytotoxic bicyclic lactone (3aS,6aR)-4,5-dimethyl-3,3a,6,6a-tetrahydro-2H-cyclopenta [b]furan-2-one 246 (Figure 9), was isolated from the ethyl acetate extract of fermentation broth of Xylaria curta 92092022 [81]. Three new lactones de-O-methyllasiodiplodins, (3R,7R)-7-hydroxy-de-O-methyllasiodiplodin 247 (Figure 9) and (3R)-5-oxo-deO-methyllasiodiplodin 248 (Figure 9), together with (3R)-7-oxo-de-O-methyllasiodiplodin 249 (Figure 9) were isolated from the co-cultivation of mangrove endophytic fungus Trichoderma sp. 307 and aquatic pathogenic bacterium Acinetobacter johnsonii B2 [10]. Two new lactones, pestalotiolactones A 250 (Figure 9) and B 251 (Figure 9), were isolated from the axenic culture of the endophytic fungus Pestalotiopsis sp., obtained from fruits of Drepanocarpus lunatus (Fabaceae) [12]. Active metabolites investigation of Talaromyces sp. (strain no. MH551540) associated with Xanthoparmelia angustiphylla afforded a new 3-methoxy-4,8-bihydroxymethyl-6-methyl-2,4,6-3en-δ-lactone, talaromycin A 252 (Figure 9) [82]. Introducing an alien carbamoyltransferase (asm21) gene into the Streptomyces sp. CS by conjugal transfer, as a result, one recombinatorial mutant named CS/asm21-4 was successfully constructed. From the extracts of the CS/asm21-4 cultured on oatmeal solid medium, a new macrolide hookerolide 253 (Figure 9) was obtained [83]. Four new aromatic butenolides, asperimides A–D 254257 (Figure 9), were isolated from solid cultures of a tropical endophytic fungus Aspergillus terreus. Compounds 254257 represent the first examples of butenolides with a maleimide core isolated from Aspergillus sp. [84]. In ongoing search for bioactive metabolites from the genus of Aspergillus, four new butenolides, namely terrusnolides A–D 258261 (Figure 9) were isolated from an endophytic Aspergillus from Tripterygium wilfordii. Compound 258 was a butenolide derived by a triple decarboxylation. Furthermore, compounds 259261 were the 4-benzyl-3-phenyl-5H-furan-2-one derivatives with an isopentene group fused to the benzene ring [85]. Chemical investigation on the culture extract of H. fuscum fermented on rice led to the isolation of one new 10-membered lactone 5,6-Epoxy-phomol 262 (Figure 9) [86]. Three new spirocyclic anhydride derivatives 263265 (Figure 9) were isolated from the endophytic fungus Talaromyces purpurogenus obtained from fresh leaves of the toxic medicinal plant Tylophora ovate [87]. A new δ-lactone penicoffeazine A, 266 (Figure 9) was isolated from Penicillium coffeae MA-314, an endophytic fungus obtained from the fresh inner tissue of the leaf of marine mangrove plant Laguncularia racemosa [77]. On the basis of One Strain/Many Compounds (OSMAC) strategy, a new natural product 267 (Figure 9), was isolated from an endophytic fungus, Phomopsis sp. sh917, harbored in stems of Isodon eriocalyx var. laxiflora [43]. A chemical investigation on metabolites of Phyllosticta sp. J13-2-12Y isolated from the leaves of Acorus tatarinowii was carried out, which led to the isolation of four new phenylisotertronic acids, R-xenofuranone B 268 (Figure 9), S-xenofuranone B 269 (Figure 9), enantio-flflavipesin B 270 (Figure 9), and S-3-hydroxy-4,5-diphenylfuran-2(5H)-one 271 (Figure 9) [88]. An endophytic fungus Pestalotiopsis microspora isolated from the fruits of Manilkara zapota was cultured in potato dextrose broth media. Chromatographic separation of the EtOAc extract of the broth and mycelium led to the isolation of a new azaphilonoid named pitholide E 272 (Figure 9) [89].

2.6. Anthraquinones

An endophytic fungus Penicillium citrinum Salicorn 46 isolated from Salicornia herbacea Torr., Produced one new citrinin derivative, pencitrinol 273 (Figure 10) [90]. Lachnum cf. pygmaeum DAOMC 250335 was obtained from ascospores originating from a collection of apothecia occurring on a dead P. rubens twig, from this strain, a new chlorinated para-quinone, chloromycorrhizinone A 274 (Figure 10) was isolated [58]. The endolichenic fungus Apiospora montagnei isolated from the lichen Cladonia sp. was cultured on solid rice medium, yielding a new xanthone derivative 8-hydroxy-3-hydroxymethyl-9-oxo-9Hxanthene-1-carboxylic acid methyl ether 275 (Figure 10) [37]. One previously undescribed metabolite anthraquinone derivative acetylquestinol 276 (Figure 10), was isolated from the culture of the endophytic fungus Eurotium chevalieri KUFA 0006 [62]. New pulvilloric acid-type azaphilones 277280 (Figure 10) were produced by Nigrospora oryzae co-cultured with Irpex lacteus [14]. A new shunt product spiciferone F 281 (Figure 10) together with two new analogs spiciferones G 282 (Figure 10) and H 283 (Figure 10) were isolated from endophytic fungus Phoma betae inhabiting in plant Kalidium foliatum (Pall.) [91]. Bioassay-guided fractionation of the dichloromethane extract of the fungus Neofusicoccum austral SYSU-SKS024 led to the isolation of three new ethylnaphthoquinone derivatives, neofusnaphthoquinone A 284 (Figure 10), 6-(1-methoxylethy1)-2,7-dimethoxyjuglone 285 (Figure 10), (3R,4R)-3-methoxyl-botryosphaerone D 286 (Figure 10), Neofusnaphthoquinone A 285 is the third example of the unsymmetrical naphthoquinone [92]. The EtOAc extract of strain Nectria pseudotrichia 120-1NP led to the identification of one new naphthoquinone, namely, nectriaquinone B 287 (Figure 10) [31]. Cytoskyrin C 288 (Figure 10), a new bisanthraquinone with asymmetrically cytoskyrin type skeleton, was isolated from an endophytic fungus ARL-09 (Diaporthe sp.) from Anoectochilus roxburghii [93]. Three new naphthomycins O–Q 289291 (Figure 10), were obtained from the solid cultured medium of recombinatorial mutant strain CS/asm21-4 (By introducing an alien carbamoyltransferase (asm21) gene into the strain Streptomyces sp. CS (CS) by conjugal transfer) [83]. From the fermentation broth of the endophytic fungus Xylaria sp.SYPF 8246, one new compound, xylarianins B 292 (Figure 10) was isolated [94]. An undescribed substituted dihydroxanthene-1,9-dione, named funiculosone 293 (Figure 10), was isolated together from the culture filtrates of Talaromyces funiculosus (Thom) Samson, Yilmaz, Frisvad & Seifert (Trichocomaceae), an endolichenic fungus isolated from lichen thallus of Diorygma hieroglyphicum (Pers.) Staiger & Kalb (Graphidaceae), in India [95]. One new dihydroxanthenone derivative globosuxanthone E 294 (Figure 10) was obtained from the crude extracts of two endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams (Sarocladium strictum) PSU-H168 and PSU-H261 which were isolated from the leaves of Hevea brasiliensis [96]. Two new naphthoquinone derivatives, 6-hydroxy-astropaquinone B 295 (Figure 10) and astropaquinone D 296 (Figure 10) were isolated from Fusarium napiforme, an endophytic fungus isolated from the mangrove plant, Rhizophora mucronata [97].

2.7. Sterides

Two new steroids, (24R)-22, 23-dihydroxy-ergosta-4,6,8(14)-trien-3-one 23-β-d-glucopyranoside 297 (Figure 11), and xylarester 298 (Figure 11), were isolated from the extract of endophytic Xylaria sp. solid culture. Compound 298 has an unprecedent ergosta skeleton with a six-membered lactonic group in A ring [98]. An endophytic fungus, Chaetomium sp. M453 isolated from Huperzia serrata (Thunb. ex Murray) Trev yield four new steroids including three unusual C25 steroids, neocyclocitrinols E–G 299301 (Figure 11), and 3β-hydroxy-5,9-epoxy-(22E,24R)-ergosta-7,22-dien-6-one 302 (Figure 11) [99]. Three new methylated Δ8-pregnene steroids, stemphylisteroids A–C 303305 (Figure 11) were isolated from the medicinal plant Polyalthia laui-derived fungus Stemphylium sp.AZGP4-2. The discovery of those three steroids is a further addition to diverse and complex array of methylated steroids [100]. Three new ergosterol derivatives, namely, fusaristerols B [(22E,24R)-3-palmitoyl-19(10→6)-abeo-ergosta-5,7,9,22-tetraen-3β-ol] 306 (Figure 11), fusaristerols C [(22E,24R)-ergosta-7,22-diene-3β,6β,9α-triol] 307 (Figure 11), and fusaristerols D [(22E,24R)-ergosta-7,22-diene-3β,5α,6β,9α-tetraol 6-acetate] 308 (Figure 11), were isolated and characterized from the endophytic fungus Fusarium sp. isolated from Mentha longifolia L. (Labiatae) roots growing in Saudi Arabia [101]. A new ergosterol derivative, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one 309 (Figure 11), was isolated from the co-culture between endophytic fungus Pleosporales sp. F46 and endophytic bacterium Bacillus wiedmannii Com1 both inhibiting in the medicinal plant Mahonia fortunei. This is the first example of isolation of a ergosterol derivative with a Δ20(22)-double bond in the side chain [102]. Two new sterol derivatives, namely ergosterimide B 310 (Figure 11) and demethylincisterol A5 311 (Figure 11), were isolated from the rice fermentation culture of Aspergillustubingensis YP-2 [103].

2.8. Other Types of Compounds

An endophytic fungus Talaromyces stipitatus SK-4 was isolated from the leaves of a mangrove plant Acanthus ilicifolius. Its crude extract exhibited significant antibacterial activity was purified to afford two new depsidones, talaromyones A and B 312313 (Figure 12) [104]. Four new amide derivatives, designated as cordycepiamides A–D 314317 (Figure 12), were isolated from the EtOAc-soluble fraction of the 95% EtOH extract of long-grain rice fermented with the endophytic fungus C. ninchukispora BCRC 31900, derived from the seeds of medicinal plant Beilschmiedia erythrophloia Hayata [105]. One new 4-hydroxycinnamic acid derivatives, methyl 2-{(E)-2-[4-(formyloxy)phenyl]ethenyl}-4-methyl-3-oxopentanoate 318 (Figure 12), was isolated from an EtOAc extract derived from a solid rice medium of endophytic fungal strain Pyronema sp. (A2-1 & D1-2) [106]. When endophytic fungus Phoma sp. nov. LG0217 isolated from Parkinsonia microphylla cultured in the absence of the epigenetic modifier, it can produced a new metabolite, (S,Z)-5-(3′,4-dihydroxybutyldiene)-3-propylfuran-2(5H)-one 319 (Figure 12) [107]. One new citrinin derivatives, pencitrin 320 (Figure 12) was isolated from an endophytic fungus P. citrinum 46 derived from Salicornia herbacea Torr by adding CuCl2 into fermentation medium [90]. Two new cytosporone derivatives 321322 (Figure 12) were isolated from the endophytic fungus Phomopsis sp. PSU-H188 [108]. Extensive chemical investigation of the endophytic fungus, Fusarium solani JK10, harbored in the root of the Ghanaian medicinal plant Chlorophora regia, using the OSMAC (One Strain Many Compounds) approach resulted in the isolation of seven new 7–desmethyl fusarin C derivatives 323329 (Figure 12) [109]. A new biphenyl derivative 5,5′-dimethoxybiphenyl-2,2′-diol 330 (Figure 12), was isolated from the mangrove endophytic fungus Phomopsis longicolla HL-2232 [110]. A new hexanedioic acid analogue, (2S,5R)-2-ethyl-5-methylhexanedioic acid 331 (Figure 12), was isolated from Penicillium sp. OC-4, an endophytic fungus associated with Orchidantha chinensis [111]. The endophytic fungus Curvularia sp. strain (M12) was isolated from a leaf of the medicinal plant Murraya koenigii and cultured on rice medium. Chromatographic analysis led to the isolation of four new compounds, murranofuran A 332 (Figure 12), murranolide A 333 (Figure 12), murranopyrone 334 (Figure 12), and murranoic acid A 335 (Figure 12) [112]. The cultivation of the mangrove-derived fungus Rhytidhysteron rufulum AS21B in acidic condition could change its secondary metabolite profile. Investigation of the culture broth extract led to the isolation and identification of two new spirobisnaphthalenes 336337 (Figure 12) [113]. On the basis of One Strain/Many Compounds (OSMAC) strategy, one new natural product 338 (Figure 12), was isolated from an endophytic fungus, Phomopsis sp. sh917, harbored in stems of Isodon eriocalyx var. laxiflora [43]. Extracts from an endophytic fungus Dendrothyrium variisporum isolated from the roots of the Algerian plant Globularia alypum yielded three new anthranilic acid derivatives 339341 (Figure 12) [60]. An endophytic fungal strain named Trichoderma atroviride was isolated from the bulb of Lycoris radiata. Following cultivation on rice medium, a novel 3-amino-5-hydroxy-5-vinyl-2-cyclopenten-1-one dimer, atricho dermone A 342 (Figure 12), was isolated. Compound 342 is the first example of cyclopentene dimer [11]. A new chaetoglobosin, penochalasin K 343 (Figure 12) bearing an unusual six-cyclic 6/5/6/5/6/13 fused ring system, was isolated from the solid culture of the mangrove endophytic fungus Penicillium chrysogenum V11 [114]. Three previously undescribed metabolites, including two prenylated indole 3-carbaldehyde derivatives 344345 (Figure 12), an anthranilic acid derivative 346 (Figure 12) were isolated from the culture of the endophytic fungus Eurotium chevalieri KUFA 0006. The structures of compounds were established as 2-(2-methyl-3-en-2-yl)-1H-indole-3-carbaldehyde (344), (2,2-dimethylcyclopropyl)-1H-indole-3-carbaldehyde (345), 2[(2,2-dimethylbut-3-enoyl)amino]benzoic acid (346) [62]. Nine previously undescribed depsidones simplicildones A–I 347355 (Figure 12) were isolated from the endophytic fungus Simplicillium sp. PSU-H41 [63]. Six new compounds including four tyrosine derivatives terezine M 356 and phomarosines A–C 357359 (Figure 12), and two new hydantoin derivatives, (S)-5-isopropyl-3-methoxyimidazolidine-2,4-dione 360 (Figure 12) and (S)-5-(4-hydroxybenzoyl)-3-isobutyrylimidazolidine-2,4-dione 361 (Figure 12), were obtained from the investigation of the endophytic fungus Phoma herbarum PSU-H256, which was isolated from a leaf of Hevea brasiliensis [115]. New mellein derivative; 4-methylmellein 362 (Figure 12) was isolated from the ethyl acetate extract of the endophytic fungus Penicillium sp. isolated from the leaf of Senecio flavus (Asteraceae) [116]. One novel cytochalasin, named jammosporin A 363 (Figure 12) was isolated from the culture of the endophytic fungus R. sanctae-cruciana, harboured from the leaves of the medicinal plant A. lebbeck [117]. An endophytic fungus Arthrinium arundinis TE-3 was isolated and purified from the fresh leaves of cultivated tobacco (Nicotiana tabacum L.). Chemical investigation on this fungal strain afforded three new prenylated diphenyl ethers 364366 (Figure 12) [118]. A novel indene derivative 367 (Figure 12), have been purified from an ethyl acetate extract of the plant-associated fungus Aspergillus flavipes Y-62, isolated from Suaeda glauca (Bunge) Bunge [119]. The endophytic fungus Mycosphaerella sp. (UFMGCB2032) was isolated from the healthy leaves of Eugenia bimarginata, a plant from the Brazilian savanna. Two novel usnic acid derivatives, mycousfuranine 368 (Figure 12) and mycousnicdiol 369 (Figure 12), were isolated from the ethyl acetate extract [120]. Intriguingly, incorporaion of Cu2+ into the PDB medium of the endophytic fungus, Anteaglonium sp. FL0768 enhanced production of metabolites and drastically affected the biosynthetic pathway resulting in the production of pentaketide dimers, palmarumycin CE4 370 (Figure 12). The structure of palmarumycin CE4 370 was established as (2β,4aα,5β,8β,8aα)-2,3,4a,5,8,8a-hexahydro-5-hydroxy-spiro [2,8-epoxynaphthalene]-1(4H)-2′-naphtho[1,8-de][1,3]dioxin-4-one [121]. Three new compounds, including rotational isomers 371372 (Figure 12) and 373 (Figure 12) were isolated from the solid cultures of the endophytic fungus Penicillium janthinellum SYPF 7899, compound 372 is the rotamer of 371 [122]. The chemical assessment of endophyte Phaeophleospora vochysiae sp. nov from Vochysia divergens, revealed a new compound 3-(sec-butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone 374 (Figure 12) [123]. Co-cultivation of fungus Bionectria sp. either with Bacillus subtilis or with Streptomyces lividans resulted in the production of two new o-aminobenzoic acid derivatives, bionectriamines A and B 375376 (Figure 12) [70]. Chemical investigation on the solid rice culture of Trichoderma atroviride S361, an endophyte isolated from Cephalotaxus fortunei, has afforded a pair of novel N-furanone amide enantiomers, (−)-trichodermadione A 377 (Figure 12) and (+)-trichodermadione A 378 (Figure 12). The structure of 377 was identified as (4′R,2E)-N-(2-ethyl-5-methyl-3-oxo-2,3-dihydrofuran-2-yl)-5-hydroxy-3-methylpent-2-enamide [17]. Secondary metabolites were isolated from the fermentation broth of the endophytic fungus Xylaria sp.SYPF 8246, including four new compounds, xylarianins A–D 379382 (Figure 12), three new natural products, 6-methox-ycarbonyl-2′-methyl-3,5,4′,6′-tetramethoxy-diphenyl ether 383 (Figure 12), 2-chlor-6-methoxycarbonyl-2′-rnethyl-3,5,4′,6′-tetramethoxy-diphenyl ether 384 (Figure 12), and 2-chlor-4′-hydroxy-6-methoxy carbonyl-2′-methyl-3,5,6′-trimethoxy-diphenyl ether 385 (Figure 12) [94]. Bysspectin A 386 (Figure 12), a polyketide-derived octaketide dimer with a novel carbon skeleton, and two new precursor derivatives, bysspectins B and C 387388 (Figure 12), were obtained from an organic extract of the endophytic fungus Byssochlamys spectabilis that had been isolated from a leaf tissue of the traditional Chinese medicinal plant Edgeworthia chrysantha [124]. Fusarithioamide B 389 (Figure 12), a new aminobenzamide derivative with unprecedented carbon skeleton was separated from Fusarium chlamydosporium EtOAc extract isolated from Anvillea garcinii (Burm.f.) DC. Leaves (Asteraceae) [125]. The study of endophytic fungus Annulohypoxylon stygium (Xylariaceae family) isolated from Bostrychia radicans algae led to the isolation of a novel compound, 3-benzylidene-2-methylhexahydropyrrolo [1,2-α] pyrazine-1,4-dione 390 (Figure 12) [126]. A new 2H-benzindazole derivative, alterindazolin A 391 (Figure 12), has been isolated from cultures of the endophyte Alternaria alternata Shm-1obtained from the fresh wild body of Phellinus igniarius. The structure of 391 was elucidated for N-benzyl-3-[p-hydroxy phenyloxygen]-benz[e]indazole [127]. One new pentenoic acid derivative, named 1,1′-dioxine-2,2′-dipropionic acid 392 (Figure 12) and a new natural product, named 2-methylacetate-3,5,6-trimethylpyrazine 393 (Figure 12), were obtained from the Cladosporium sp. JS1-2, an endophytic fungus isolated from the mangrove Ceriops tagal collected in South China Sea [128]. Chemical assessment of the new species Diaporthe vochysiae sp. nov. (LGMF1583), isolated as endophyte of the medicinal plant Vochysia divergens, revealed two new carboxamides, vochysiamides A 394 (Figure 12) and B 395 (Figure 12) [129]. Two new eremophilane derivatives lithocarins B 396 (Figure 12) and 397 (Figure 12), were isolated from the endophytic fungus Diaporthe lithocarpus A740 [41]. Five new cytochalasans 398402 (Figure 12) were isolated from the rice fermentation of fungus Xylaria longipes isolated from the sample collected at Ailao Moutain [130]. A new compound which was determined as 10-Ethylidene-2,4,9-trimethoxy-10,10a-dihydro-7,11-dioxa-benzo[b]heptalene-6,12-dione 403 (Figure 12) was isolated from Penicillium citrinum inhabiting Parmotrema sp. [131]. Investigation of the culture broth of Periconia macrospinosa KT3863 led to discover two new chlorinated melleins (3R,4S)-5-chloro-4-hydroxy-6-methoxymellein 404 (Figure 12), (R)-7-chloro-6-methoxy-8-O-methylmellein 405 (Figure 12) [132]. Two new compounds, lasdiplactone 406 (Figure 12) and lasdiploic acid 407 (Figure 12) were isolated from the chloroform extract of cell free filtrate of the endophytic fungus Lasiosdiplodia pseudotheobromae. The structure of 406 was characterized as (3S,4S,5R)–4–hydroxymethyl–3,5–dimethyldihydro–2–furanone [133]. Studies on the bioactive extract of mangrove endophytic fungus Pleosporales sp. SK7 led to the isolation of one new asterric acid derivative named methyl 2-(2-carboxy-4-hydroxy-6-methoxylphenoxy)-6-hydroxy-4-methyl-benzoate 408 (Figure 12) [23]. Chemical investigation of the mangrove-derived fungus Aspergillus sp. AV-2 following fermentation on solid rice medium led to the isolation of a new phenyl pyridazine derivative 409 (Figure 12) and a new prenylated benzaldehyde derivative, dioxoauroglaucin 410 (Figure 12) [134]. Three new furan derivatives, irpexlacte B–D 411413 (Figure 12), were isolated from the endophytic fungus Irpex lacteus DR10-1 waterlogging tolerant plant Distylium chinense. Structures of compounds 411413 were established as 5-(2α-hydroxypentyl) furan-2-carbaldehyde, 5-(1α-hydroxypentyl) furan-2-carbaldehyde, 5-(5-(2-hydroxypropanoyl) furan-2-yl) pentan-2-one, respectively [24]. Four new alkyl aromatics, penixylarins A–D 414417 (Figure 12), were isolated from a mixed culture of the Antarctic deep-sea-derived fungus Penicillium crustosum PRB-2 and the mangrove-derived fungus Xylaria sp. HDN13-249. UPLC-MS data and an analysis of structural features showed that compounds 414 and 415 were produced by collaboration of the two fungi, while compounds 416417 could be produced by Xylaria sp. HDN13-249 alone, but noticeably increased quantities by co-cultivation [135]. The co-culture of marine red algal-derived endophytic fungi Aspergillus terreus EN-539 and Paecilomyces lilacinus EN-531 induced the production of a new terrein derivative, namely asperterrein 418 (Figure 12) [136]. Fractionation and purification of the ethyl acetate extract of Diaporthe lithocarpus, an endophytic fungus from the leaves of Artocarpus heterophyllus, yielded one new compound, diaporthindoic acid 419 (Figure 12) [137]. A new diketopiperazine cyclo-(L-Phe-N-ethyl-L-Glu) 420 (Figure 12), was isolated from the cultures of an endophytic fungus Aspergillus aculeatus F027 [138]. Four novel compounds with g-methylidene-spirobutanolide core, fusaspirols A–D 421424 (Figure 12), were isolated from the brown rice culture of Fusarium solani B-18. Compound 422 was found as the regioisomer of 421 [139]. One new polyacetylene glycoside 425 (Figure 12), one new brasilane-type sesquiterpenoid glycoside 426 (Figure 12), and two novel isobenzofuran-1(3H)-one derivatives 427428 (Figure 12) were isolated from the solid culture of the endolichenic fungus Hypoxylon fuscu [86]. Chemical investigation of the crude extracts of both endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261 resulted in the isolation of three new compounds including two depsidones, simplicildones J and K 429430 (Figure 12) and one dihydroxanthenone derivative, globosuxanthone E 431 (Figure 12) [96]. The apple juice supplemented solid rice media led to significant changes in the secondary metabolism of the endophytic fungus, Clonostachys rosea B5-2, and induced the production of four new compounds, (−)-dihydrovertinolide 432 (Figure 12), and clonostach acids A 433 (Figure 12), B 434 (Figure 12), and C 435 (Figure 12) [140]. Six new nonadride derivatives 436441 (Figure 12) were isolated from the endophytic fungus Talaromyces purpurogenus obtained from fresh leaves of the toxic medicinal plant Tylophora ovate [87]. One new cyclic tetrapeptide, 18-hydroxydihydrotentoxin 442 (Figure 12), and a new amide, 6-hydroxyenamidin 443 (Figure 12) were obtained from the endophytic fungus Phomopsis sp. D15a2a isolated from the plant Alternanthera bettzickiana [55]. From an endophytic microorganism, Aureobasidium pullulans AJF1, harbored in the flowers of Aconitum carmichaeli, two unique lipid type new compounds (3R,5R)-3-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-5-hydroxydecanoic acid 444 (Figure 12), and (3R,5R)-3-(((3R,5R)-5-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-3-hydroxydecanoyl)oxy)-5-hydroxydecanoic acid 445 (Figure 12) were obtained [141]. The fungal strain Alternaria alternata JS0515 was isolated from Vitex rotundifolia (beach vitex). From the gungus one new altenusin derivative 446 (Figure 12), was isolated [142]. An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation three aryl esters 447449 (Figure 12) [27].

3. Biological Activity

3.1. Antimicrobial Activity

3.1.1. Antifungal Activity

New polyketide-terpene hybrid metabolites 1 and 5 were tested for their inhibition activity following the NCCLS recommendations against six phytopathogenic fungi Botrytis cinerea (ACCC 37347), Verticillium dahliae (ACCC 36916), Fusarium oxysporum (ACCC 37438), Alternaria solani (ACCC 36023), Fusarium gramineum (ACCC 36249), and Rhizoctonia solani (ACCC36124) obtained from Agricultural Culture Collection of China (ACCC). The antifungal assay displayed that 1 and 5 exhibited pronounced biological effects against F. oxysporum with MIC (minimum inhibitory concentration) value of 8 g/mL, whereas 5 can potently inhibited F. gramineum at concentration of 8 g/mL, compared with the positive control ketoconazole (MIC value of 8 g/mL) [9].
Compounds 1516 were evaluated for antifungal activities against six fungal strains, including Rhizoctonia solani, Verticillium dahliae Kleb, Helminthosporium maydis, Fusarium oxysporum, Botryosphaeria berengeriana and Colletotrichum acutatum Simmonds. Both compounds displayed moderate activities against three fungal strains Verticillium dahliae Kleb, Helminthosporium maydis, and Botryosphaeria dothidea with MIC values of 25–50 μg/mL [15].
The inhibitory activities of compounds 1720 against four phytopathogenic fungi, including Phytophthora infestane (late blight), Alternaria solani (early blight), Rhizoctonia solani (black scurf), Fusarium oxysporum (blast), were evaluated. Compounds 1720 all showed potent inhibitory activities toward A. solani and F. oxysporum with MIC value of 16 μg/mL, 32 μg/mL, 8 μg/mL, 8 μg/mL and 32 μg/mL, 16 μg/mL, 16 μg/mL, 16 μg/mL, respectively, while 1920 weakly inhibited P. infestans and R. solani with MIC value of 128 μg/mL, 64 μg/mL and 128 μg/mL, 32 μg/mL, respectively. Hygromycin B was used as Positive control (MIC values of P. infestans, A. solani, R. solani, and F. oxysporum were 8 μg/mL, <4 μg/mL, 8 μg/mL, 64 μg/mL, respectively) [16].
Antifungal activity of compounds 5055 against 14 plant-pathogenic fungi Alternaria solani QDAU-14 (AS), Bipolaris sorokiniana QDAU-7 (BS), Ceratobasidium cornigerum QDAU-8 (CC), C. gloeosporioides Penz QDAU-9 (CG), Fusarium graminearum QDAU-10 (FG), F. oxysporum f. sp. cucumebrium QDAU-16 (FOC), F. oxysporum f. sp. momordicae QDAU-17 (FOM), F. oxysporum f. sp. radicis lycopersici QDAU-5 (FOR), F. solani QDAU-15 (FS), Glomerella cingulate QDAU-2 (GC), Helminthosporium maydis QDAU-18 (HM), Penicillium digitatum QDAU-11 (PD), P. piricola Nose QDAU-12 (PP), and Valsa mali QDAU-13 (VM) were carried out by the microplate assay. Compound 50 exhibited inhibitory activity against the 13 test fungi with MIC values of 4 μg/mL (AS), 1 μg/mL (BS), 16 μg/mL (CC), 8 μg/mL (CG), 8 μg/mL (FG), 1 μg/mL (FOC), 2 μg/mL (FOM), 64 μg/mL (FOR), 4 μg/mL (FS), 1 μg/mL (GC), 8 μg/mL (PD), 4 μg/mL (PP), 16 μg/mL (VM), respectively, while compounds 5055 showed activity against Fusarium oxysporum f. sp. cucumebrium with MIC values ranging from 1 to 64 μg/mL. 51 exhibited inhibitory activity against the 6 test fungi with MIC values of 32 μg/mL (AS), 8 μg/mL (BS), 32 μg/mL (FS), 4 μg/mL (GC), 8 μg/mL (PD), 4 μg/mL (PP), respectively. 52 exhibited inhibitory activity against the 4 test fungi with MIC values of 64 μg/mL (FOR), 1 μg/mL (GC), 8 μg/mL (PP), 32 μg/mL (VM), respectively. 53 exhibited inhibitory activity against the 3 test fungi with MIC values of 64 μg/mL (FOR), 16 μg/mL (PD), 1 μg/mL (PP), respectively. 54 exhibited inhibitory activity against Helminthosporium maydis with MIC value of 16 μg/mL. 55 exhibited inhibitory activity against P. piricola Nose with MIC values of 4 μg/mL (AS). Amphotericin B was used as the positive control against fungi with MIC values of 2 μg/mL (AS), 0.5 μg/mL (BS), 8 μg/mL (CC), 0.5 μg/mL (CG), 2 μg/mL (FG), 0.5 μg/mL (FOC), 1 μg/mL (FOM), 2 μg/mL (FOR), 4 μg/mL (FS), 0.5 μg/mL (GC), 2 μg/mL(HM), 2 μg/mL (PD), 2 μg/mL (PP), 8 μg/mL (VM), respectively [25].
Compounds 6874 were assayed for their antifungal activities against C. albicans. Geneticin (G418), was used as positive control with the MIC value of 6.3 μg/mL. Compound 69 displayed inhibitory effect against C. albicans with an MIC value of 12.5 μg/mL, while compounds 68 and 74 exhibited weak inhibitory effect against C. albicans with MIC values of 100 μg/mL and 150 μg/mL [32].
Antifungal activities (Minimum inhibitory concentrations; MICs) of the isolated metabolite 170 were determined using a serial dilution assay against Mucor hiemalis DSM 2656. Compound 170 showed moderate to weak antifungal activity against Mucor hiemalis DSM 2656 with a MIC value of 33.33 μg/mL [52].
One fungus Candida albicans (ATCC 10231) was used for antifungal tests, the results showed that compound 177 exhibited significant antifungal activity against C. albicans with the MIC value of 2.62 μg/mL. The positive control for antifungal tests was used by ketoconazole with MIC value of 0.10 μg/mL [54].
The methylated dihydropyrone 189 and compound 274 were tested for in vitro antifungal activity using the Oxford diffusion assay against M. violaceum (Microbotryum violaceum) and S. cerevisiae (Saccharomyces cerevisiae), 189 and 274 exhibited moderate antifungal activity, inhibiting the growth of S. cerevisiae and M. violaceum at 25 μg/mL. Nystatin was the positive control for antifungal assays, previous studies had shown the MIC values of nystatin in the S. cerevisiae culture used was 4 µg/mL and for M. violaceum was 2 µg/mL [58].
Minimum Inhibitory Concentration (MIC) assays were used to assess antifungal activity of the compounds against anti-phytopathogenic activity against seven pathogenic fungi Alternaria alternata (Aa), Botrytis cinerea (Bc), Cochliobolus heterostrophus (Ch), Colletotrichum lagenarium (Cl), Fusarium oxysporum (Fo), Gaeumannomyces graminis (Gg), and Thielaviopsis basicola (Tb). Compound 227 showed potent and specific activity against 4 fungi with MIC values of 32 μg/mL(Bc), 16 μg/mL(Ch), 8 μg/mL(Fo), 8 μg/mL(Tb), respectively, whereas compound 228 showed moderate activity against 3 fungi with MIC values of 16 μg/mL(Bc), 32 μg/mL(Ch), 32 μg/mL(Fo) respectively. Prochloraz, a commercialized broad-156 spectrum fungicide widely used in agriculture, was used as positive antifungal control with MIC values of 8 μg/mL(Bc), 16 μg/mL(Ch), 8 μg/mL(Fo), 8 μg/mL(Tb), respectively. To the best of our knowledge, this is the first study to show that PIAs exhibit inhibitory activity against plant-pathogenic fungi [74].
Prochaetoviridin A 230 was evaluated for its antifungal activities against 5 pathogenic fungi S. sclerotiorum, B. cinerea, F. graminearum, P. capsici and F. moniliforme at the concentration of 20 µg/mL. It showed moderate antifungal activity with inhibition rates ranging from 13.7% to 39.0% [69].
Compounds 244 and 245 were evaluated against phytopathogenic fungi Cladosporium cladosporioides and C. sphaerospermum (Cladosporium sphaerospermum) using direct bioautography. The results showed that 244 exhibited antifungal activity, with a detection limit of 5 μg, for both fungi, while compound 245 displayed weak activity (detection limit > 5 μg), with a detection limit of 25 μg. Nystatin was used as a positive control, showing a detection limit of 1 μg [80].
Compound 266 was tested for antimicrobial activities against two plant-pathogenic fungi Fusarium oxysporum f. sp. momordicae nov. f. and Colletotrichum gloeosporioides, and exhibited potent activity against both strains with MIC values of 5 µM, which was close to that of the positive control, amphotericin B (MIC = 0.5 µM) [77].
Compounds 289291 were assayed for antifungal activity against phytopathogenic fungi M. grisea and F. verticillioides, they showed evident inhibition of phytopathogenic fungi. The MIC values of compounds 289291 were 200 μg/mL, 50 μg/mL and 50 μg/mL against M. Grisea and 200 μg/mL, 100 μg/mL and 100 μg/mL against F. verticillioides. Hygromycin B was the positive control against fungus with the MIC values of 50 μg/mL against both M. Grisea and F. verticillioides [83].
The purified metabolite 293 was tested for antimicrobial activity against selected pathogens namely C. albicans. Funiculosone (293) displayed antimicrobial activity inhibiting fungal pathogens. Funiculosone was able to inhibit the growth of C. albicans with an IC50 (50% inhibitory concentration) of 35 μg/mL [95].
Antifungal activity was determined against C. neoformans ATCC90113. The results showed that globosuxanthone E 294 displayed antifungal activity against Cryptococcus neoformans ATCC90113 with the MIC value of 32 μg/mL. Amphotericin B was used as a positive control for antifungal activity and exhibited an MIC value of 0.5 μg/mL [96].
The new compound, penochalasin K 343 was tested for its antifungal activity against four phytopathogenic fungi including C. musae, C. gloeosporioides, P. italicm, and R. solani. Compound 343 displayed excellent selective activities against the two phytopathogenic fungi Colletotrichum gloeosporioides (Penz) Sacc. (C. gloeosporioides), and Rhizoctonia solani Kühn (R. solani), with MIC values of 6.13 µM and 12.26 µM, respectively. Moreover, the activity towards C. gloeosporioides and R. solani were about ten-fold and two-fold better than those of the positive control carbendazim, respectively. Whereas only moderate or weak inhibitory activities were exhibited by compound 343 towards Colletotrichum musae (Berk. and M. A. Curtis) Arx. (C. musae) and Penicillium italicum Wehme (P. italicm). Carbendazim and the solvent were adopted as positive and negative control, respectively. The MIC values of Carbendazim against C. gloeosporioides, R. solani, C. musae and P. italicm were 65.38 µM, 32.69 µM, 32.69 µM and 16.34 µM [114].
The isolated compound 349 was evaluated for antifungal activities against C. neoformans and P. marneffei, it displayed weak antifungal activity against C. neoformans with MIC value of 32 μg/mL. Amphotericin B was used as positive control for fungi, displayed the MIC values of 1.0 μg/mL and 2.0 μg/mL against C. neoformans and P. marneffei [63].
Three fungi (Aspergillus flavus, Fusarium oxysporum and Candida albicans) were used in antifungal activity tests by disk diffusion method, the antifungal activity was recorded as clear zones of inhibition surrounding the disc (mm). Compound 362 showed antifungal activity against F. oxysporum (zone of inhibition was 6 mm) and variable activities against A. flavus and the yeast C. albicans (zone of inhibition was 5 mm). Nystatin (10 mg/disc) was used as standard antifungal (zone of inhibition against A. flavus and F. oxysporum were 12 mm and 17 mm) [116].
The antifungal activity against six commonly occurring plant-pathogenic fungi Alternaria alternata, Cochliobolus heterostrophus, Gaeumannomyces graminis, Glomerella cingulata, Mucor hiemalis, and Thielaviopsis basicola of compounds 364365 were evaluated. Compounds 364 and 365 showed selective antifungal activity against Mucor hiemalis with minimum inhibitory concentration (MIC) values of 8 µg/mL and 4 µg/mL, respectively. Prochloraz was used as positive control with MIC value of 8 µg/mL against Mucor hiemalis [118].
In search for novel antifungal compounds, 368 and 369 were tested against C. neoformans and C. gattii. Compounds 368 and 369 exhibited moderate antifungal activities against Cryptococcus neoformans and Cryptococcus gattii, each with minimum inhibitory concentration values of 50.0 μg/mL and 250.0 μg/mL, respectively [120].
The antifungal activity of the compound 374 were evaluated against fungal strains Phyllosticta citricarpa LGMF06 and Colletotrichum abscissum LGMF1268 in order to select the best culture conditions to produce bioactive secondary metabolites. The isolated compound 374 displayed antifungal activity against the citrus phytopathogen Phyllosticta citricarpa with the inhibition zone of 30 mm. Amphotericin B was used as positive control with the inhibition zone of 37 mm [123].
The antifungal effect of 389 was assessed by agar disc diffusion assay towards Candida albicans (AUMC No. 418), Geotrichium candidum (AUMC No. 226), and Trichophyton rubrum (AUMC No. 1804) as fungi. It exhibited selective antifungal activity towards C. albicans (MIC 1.9 µg/mL and IZD 14.5 mm), comparing to the antifungal standard clotrimazole (MIC 2.8 µg/mL and IZD 17.9 mm), whilst, it had moderate activity against G. candidum (MIC 6.9 µg/mL and IZD 28.9 mm) [125].
Compound 418 was tested for antimicrobial activities against five plant-pathogenic fungi A. brassicae, Colletotrichum gloeosprioides, Fusarium oxysporum, Gaeumannomyces graminis, and P. piricola. It exhibited inhibitory activity against A. brassicae and P. piricola with the same MIC value of 64 µg/mL. The positive control against A. brassicae and P. piricola was amphotericin B with MIC values of 4 µg/mL and 8 µg/mL respectively [136].
Antifungal activity was determined against C. neoformans ATCC90113. Simplicildone K 430 and globosuxanthone E 431 displayed weak antifungal activity against Cryptococcus neoformans ATCC90113 with the same MIC values of 32 μg/mL. Amphotericin B was used as a positive control for antifungal activity and exhibited an MIC value of 0.5 μg/mL against C. neoformans ATCC90113 [96].

3.1.2. Antibacterial Activity

The new compound 9 was evaluated for its antibacterial activities against Mycobacterium tuberculosis, Staphylococcus aureus (ATCC25923), S. aureus (ATCC700699), Enterococcus faecalis (ATCC29212), E. faecalis (ATCC51299), E. faecium (ATCC35667), E. faecium (ATCC700221) and Acinetobacter baumannii (ATCCBAA1605). It showed very weak inhibitory effect against M. tuberculosis (MIC > 50 µM) [12].
Compounds 1516 were also evaluated for their antibacterial activity against twelve bacteria strains, including Micrococcus lysodeikticus, Bacillus subtilis, Bacillus cereus, Micrococcus luteus, Staphyloccocus aureus, Bacillus megaterium, Bacterium paratyphosum B, Proteusbacillm vulgaris, Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter aerogenes. Compounds 1516 displayed moderate activities against three bacterial strains (Bacillus subtilis, Bacillus cereus and Escherichia coli) with MIC values of 25–50 μg/mL [15].
Compounds 2324, 26 and 28 were evaluated for their antimicrobial activities against the Gram-positive strains Staphylococcus aureus ATCC 25923 and Mycobacterium smegmatis ATCC 607, Gram-negative strains Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027, by the liquid growth inhibition in 96-well microplates. Compounds 2324, 26 and 28 displayed mild antibacterial activities against the Gram positive strain Staphylococcus aureus ATCC 25923 with IC50 values ranging from 31.5 to 41.9 µM [18].
New compounds 49, 411413 were evaluated for antibacterial activity against P. aeruginosa (CMCC(B)10,104). Compared with the positive control (Gentamicin, 0.18 µM), compounds 49, 411413 showed moderate activity with MIC values of 24.1 µM, 32.3 µM, 35.5 µM and 23.8 µM respectively [24].
Antimicrobial evaluation against one human pathogen Escherichia coli EMBLC-1 (EC), 10 marine-derived quatic bacteria Aeromonas hydrophilia QDIO-1 (AH), Edwardsiella tarda QDIO-2 (ET), E. ictarda QDIO-10, Micrococcus luteus QDIO-3 (ML), Pseudomonas aeruginosa QDIO-4 (PA), Vibrio alginolyticus QDIO-5, V. anguillarum QDIO-6 (VAn), V. harveyi QDIO-7 (VH), V. parahemolyticus QDIO-8 (VP), and V. vulnificus QDIO-9 (VV), was carried out by the microplate assay. Compound 50 showed activity with the same MIC value of 8 µg/mL against 4 bacteria ((EC) (AH) (PA) and (VH)) and the value of 4 µg/mL against V. parahemolyticus. Compound 51 showed activity with the MIC values of 16 µg/mL (EC), 8 µg/mL (PA) and 16 µg/mL (VH). Compound 52 showed activity with the MIC values of 8 µg/mL (EC), 8 µg/mL (AH), 4 µg/mL (PA), 2 µg/mL (VH) and 8 µg/mL (VP). While compound 55 had activity against aquatic pathogens Edwardsiella tarda and Vibrio anguillarum with MIC values of 1 μg/mL and 2 μg/mL, respectively, comparable to that of the positive control chloramphenicol (2 µg/mL (EC), 4 µg/mL (AH), 0.5 µg/mL (ET), 4 µg/mL (ML), 2 µg/mL (PA), 1 µg/mL (VAn), 1 µg/mL (VH), 4 µg/mL (VP), 1 µg/mL (VV)) [25].
Compounds 66 and 116 were evaluated for their antimicrobial activities against three human pathogenic strains (Escherichia coli ATCC 25922, Staphyloccocus aureus ATCC 25923 and Candida albicans ATCC 10231) by microbroth dilution method in 96-well culture plates. Bioassay results indicated that compound 116 displayed potent activity against Staphyloccocus aureus with an MIC value of 6.25 µM, which was equal to that of ampicillin sodium as a positive control, and compound 66 had a moderate inhibitory effect on S. aureus with an MIC value of 25.0 µM [30].
Compounds 70 and 74 were assayed for their antimicrobial activities against S. aureus, B. cereus, B. subtillis, P. aeruginosa, and K. pneumonia. The results showed that compounds 70 and 74 displayed weak antimicrobial effects with the same MIC value of 100 µg/mL against B. subtillis and S. aureus. Ampicillin was used as positive control with MIC values of 8 µg/mL and 3.5 µg/mL against S. aureus and B. subtillis [32].
Compound 119 was evaluated for antibacterial activities in vitro against Gram-Positive and Gram-Negative Bacteria (Staphylococcus aureus (DSM 799), Escherichia coli (DSM 1116), Escherichia coli (DSM 682), Bacillus subtilis (DSM 1088) and Acinetobacter sp. (DSM 586)). It was active against Staphylococcus aureus with an MIC value of 0.1 μg/mL. Streptomycin and Gentamicin were used as references against Staphylococcus aureus with MIC values of 5.0 μg/mL and 1.0 μg/mL, respectively. Comparison of 119 with 118 (>10.0 µg/mL against Staphylococcus aureus) and confirmed that the substitution at C-11 plays an important role in increasing the antibacterial activity against the selected bacterium [42].
The antibacterial activity of 157 and 159 was evaluated against five pathogenic bacteria of Micrococcus tetragenus, Staphylococcus aureus, Streptomyces albus, Bacillus cereus, and Bacillus subtilis. Compound 157 showed potent antimicrobial activity against B. cereus with the MIC value of 12.5 µg/mL, Compound 159 also showed potent antimicrobial activities against B. subtilis, S. aureus, and S. albus with the same MICs value of 12.5 µg/mL. Ciprofloxacin was used as a positive control with MIC values of 6.15 µg/mL, 5.60 µg/mL, 0.20 µg/mL, 1.50 µg/mL and 6.15 µg/mL against M. tetragenus, B. cereus, B. subtilis, S. aureus and S. albus [49].
The antimicrobial activity was determined by the paper disk diffusion method (100 μg compound in 8 mm paper disk), using meat peptone agar for Staphylococcus aureus and Pseudomonas aeruginosa, peptone yeast agar for Candida albicans, and potato dextrose agar for Aspergillus clavatus. 164 showed moderate antibacterial activity against Staphylococcus aureus NBRC 13276 (5: 24 mm) at a concentration of 100 μg/disk (MIC value: 3.2 μg/mL). Chloramphenicol was used for positive control against S. aureus (1 μg/mL) [50].
Antimicrobial activities (Minimum inhibitory concentrations; MICs) of the isolated metabolite 170 was determined using a serial dilution assay against Bacillus subtilis DSM 10, Chromobacterium violaceum DSM 30191, Escherichia coli DSM 1116, Micrococcus luteus DSM 1790, Pseudomonas aeruginosa DSM PA14, Staphylococcus aureus DSM 346, and Mycobacterium smegmatis DSM ATCC700084. Compound 170 showed moderate antibacterial activity against Staphylococcus aureus DSM 346 and Bacillus subtilis DSM 10, respectively, with a MIC value of 33.33 μg/mL. Oxytetracyclin was used as positive control with MIC values of 0.2 μg/mL and 4.16 μg/mL against Staphylococcus aureus DSM 346 and Bacillus subtilis DSM 10, respectively [52].
Antimicrobial tests were used for the disc diffusion method. Two Gram-positive methicillin-resistent Staphylococcus aureus, Bacillus subtilis (ATCC 6633), two Gram-negative pseudomonas aeruginosa (ATCC 9027), Salmonella typhimurium (ATCC 6539), were used. Compound 176 showed strong antibacterial activity against the P. aeruginosa and MRSA with the MIC values of 1.67 µg/mL and 3.36µg/mL, respectively. Compound 177 exhibited significant antibacterial activity against B. subtilis with the MIC value of 5.25 µg/mL. Positive control for antifungal tests were used by Ampicillin with the MIC values of 0.15 µg/mL, 0.15 µg/mL and 0.07 µg/mL against P. aeruginosa, MRSA (Methicillin-resistant Staphylococcus aureus) and B. subtilis, respetively. The results indicated that the methylester displayed improved biological activity and showed a selective antibacterial activity against P. aeruginosa and MRSA. Compound 176 exhibited more strong antimicrobial activity than compound 177 [54].
Antibacterial activity was determined against five pathogenic bacteria Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Bacillus cereus (ATCC 11778), Staphyloccocus epidermidis (ATCC 12228) and Staphylococcus albus (ATCC 8799) by the microplate assay method. Compound 208 showed weak antibacterial activity against Staphylococcus aureus with a MIC value of 20 μg/mL. Ciprofloxacin was used as the positive control [66].
Antimicrobial activity testing of the compound 212 was carried out against a set of microorganisms using paper-disk diffusion assay. 212 exerted moderate-high activities (13 mm, 16 mm, 15 mm, 10 mm, 11 mm and 14 mm) against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Saccharomyces cerevisiae, Bacillus cereus and Bacillus subtilis ATCC 6633. Gentamycin was used as positive control with the diameter of agar diffusion of 22 mm, 18 mm, 17 mm, 23 mm, 20 mm and 18 mm against the 5 bacteria as mentioned above [68].
Minimum Inhibitory Concentration (MIC) assays were used to assess antibacterial activity of the isolated compounds 227228 against human pathogens (Escherichia coli, Micrococcus luteus, and Pseudomonas aeruginosa) and plant pathogen (Ralstonia solanacearum). Chloromycetin was used as a positive antibacterial control. Notably, compound 227 demonstrated potent activity against P. aeruginosa with an MIC value of 1 μg/mL, which was better than that of the positive control chloromycetin (MIC = 4 μg/mL). Compound 228 displayed activity against Micrococcus luteus and Pseudomonas aeruginosa with the same MIC value of 8 μg/mL (2 μg/mL and 4 μg/mL against Micrococcus luteus and Pseudomonas aeruginosa for Chloromycetin). In contrary to compounds 228 and the known compound A (Figure 13), B (Figure 13) showed stronger antibacterial activity (MIC values of 4, 4, 8, and 8 μg/mL against E. coli, M. luteus, P. aeruginosa, and R. solanacearum, respectively), indicating that hydroxylation at C-10 can augment antibacterial activity [74].
Compound 229 was tested for in vitro antimicrobial activity against 2 bacteria B. subtilis (ATCC 23857), and E. coli (ATCC 67878). Chloramphenicol was the antibacterial positive control. 229 showed modest antibiotic activity to E. coli with an MIC value of 100 µg/mL [58].
Antimicrobial activities were determined against four terrestrial pathogenic bacteria, including Pseudomonas aeruginosa, Methicillinresistant Staphylococcus aureus, Bacillus subtilis and Escherichia coli by the microplate assay method. Compound 231 exhibited modest antibacterial activity against Escherichia coli and Pseudomonas aeruginosa with 12.5 µg/mL, 50 µg/mL, respectively [75].
Antimicrobial activity was estimated by the inhibitory zone to five indicator microorganisms (Bacillus subtilis CMCC 63501, Candida albicans CMCC 98001, Escherichia coli CMCC 44102, Pseudomonas aeruginosa CMCC 10104 and Staphylococcus aureus CMCC 26003). Compounds 237 and 238 exhibited growth inhibitory activity against E. coli with MIC values of 32 µg/mL. Chloramphenicol was used as positive control with an MIC value of 4 µg/mL against E. coli [76].
Compound 241 was tested for antibacterial activity against Bacillus subtilis (ATCC 6633), Staphylococcus aureus (CGMCC 1.2465), Streptococcus pneumoniae (CGMCC 1.1692), Escherichia coli (CGMCC 1.2340), the results showed that 241 displayed modest antibacterial activity against B. subtilis with MIC value of 66.7 µM (the positive control gentamycin showed MIC value of 1.3 µM) [78].
Compound 246 was evaluated by the agar diffusion method against Gram-positive and Gram-negative bacteria, 246 showed moderate antibacterial activity against both Pseudomonas aeruginosa ATCC 15442 (13 mm) and Staphylococcus aureus NBRC 13276 (13 mm), respectively, at a concentration of 100 μg/disk [81].
Compounds 253, 289291 were assayed for their antibacterial activities against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium. All of the four compounds exhibited antibacterial activities against Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus with the same MIC values of 25 µg/mL, 50 µg/mL and 25 µg/mL, respectively. Ampicillin was the positive control against bacteria, the MIC of ampicillin was lower than 0.78 μg/mL against Salmonella typhimurium, and Staphylococcus aureus, while the MIC value against Escherichia coli was 100 µg/mL [83].
The antimicrobial activity was determined by the paper disk diffusion method (100 μg compound in 8 mm paper disk), using meat peptone agar for Staphylococcus aureus and Pseudomonas aeruginosa. Comound 287 exhibited antibacterial activity against S. aureus and P. aeruginosa with MIC values (μg/mL) of >50 and 6.25. Chloramphenicol and kanamycin were used for positive control against S. aureus and P. aeruginosa (each 1 μg/mL), respectively [31].
Compound 293 was tested for antimicrobial activity against selected pathogens namely S. aureus, E. coli and Pseudomonas aeruginosa C. Gessard. Funiculosone (293) displayed antimicrobial activity inhibiting the bacterial pathogens. Funiculosone was able to inhibit the growth of E. coli, S. aureus and C. albicans with IC50 of 25 μg/mL and 58 μg/mL and 35 μg/mL respectively [95].
Compounds 295296 were evaluated for antimicrobial activity against Gram-positive and Gram-negative bacteria. Compounds 295 and 296 showed moderate antibacterial activity against S. aureus NBRC 13276 and P. aeruginosa ATCC 15442 (MIC values of 6.3 µg/mL and 12.5 µg/mL for S. aureus NBRC 13276, 6.3 µg/mL and 6.3 µg/mL for P. aeruginosa ATCC 15442) [97].
Compounds 303304 were evaluated for their antibacterial activities against six pathogenic bacteria including M. tetragenus, S. aureus, S. albus, B. cereus, B. subtilis, E. coli. Compound 303 showed antibacterial activity against E. coli with the MIC value of 6.25 μg/mL, and 304 exhibited a broad spectrum of antibacterial activities against six pathogenic with the MIC value ranging from 12.5 to 50 μg/mL (MIC values: 50 µg/mL for M. tetragenus, 25 µg/mL for S. aureus, >50 µg/mL for S. albus, 25 µg/mL for B. cereus, 12.5 µg/mL for B. subtilis and 50 µg/mL for E. coli). Ciprofloxacin was used as a positive control (MIC values: 0.313 µg/mL for M. tetragenus and S. aureus, 0.625 µg/mL for S. albus, B. cereus, B. subtilis and E. coli) [100].
The antibacterial activities of pure compound 309 was evaluated against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis and Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli using the disk diffusion assay. The new compound 309 showed inhibitory activity against S. aureus at 0.04 µg/paper disk, and the diameter of inhibition zone was 0.71 cm. The MIC for compound 309 against S. aureus was 100 µg/mL using the broth microdilution method, while streptomycin was employed as the positive control with an MIC of around 50 µg/mL [102].
Two Gram-positive bacteria Bacillus subtilis (ATCC6633) and Staphylococcus aureus ATCC (25923) were used. The antibacterial assay and the determination of the minimum inhibitory concentration (MIC) were determined according to continuous dilution method in the 96-well plates. Compound 313 showed antibacterial activity against Bacillus subtilis with an MIC value of 12.5 μg/mL. Ciprofloxacin was the positive control [104].
Compound 318 was tested for antibacterial activity against Mycobacterium marinum ATCCBAA-535. Although rifampin as positive control showed significantly in vitro antibacterial activity against Mycobacterium marinum ATCCBAA-535 with IC50 of 2.1 µM, compound 318 also exhibited potential inhibitory activity with IC50 of 64 µM [106].
The antibacterial activities of the isolated compounds 325329 were evaluated against the soil bacterium Acinetobacter sp. BD4 (Gram–negative), the environmental strain of Escherichia coli (Gram–negative), as well as human pathogenic strains of Staphylococcus aureus (Gram–positive) and Bacillus subtilis (Gram–positive). The standard references employed were streptomycin (MIC values: 1.0 µg/mL against Escherichia coli, 10.0 µg/mL against Acinetobacter sp. BD4) and gentamicin (MIC values: 1.0 µg/mL against Escherichia coli, 5.0 µg/mL against Acinetobacter sp. BD4). Compounds 325326 and 328, demonstrated pronounced activity at 10.0 μg/mL against the soil bacterium Acinetobacter sp. BD4 comparable to streptomycin. Compounds 327 and 329 displayed antibacterial efficacies against Escherichia coli with the same MIC value of 5.0 µg/mL [109].
Antibacterial activity of the new compound 330 against Vibrio parahaemolyticus and Vibrio anguillarum was determined by the conventional broth dilution assay. 330 showed moderate inhibitory effects on Vibrio parahaemolyticus with an MIC value of 10 μg/mL. Ciprofloxacin was used as a positive control [110].
Antibacterial efficacies of the metabolite 339 were determined by serial dilution assay. Compound 339 showed strong activity against Bacillus subtilis and Micrococcus luteus with MIC values of 8.33 µg/mL and 16.66 µg/mL, respectively, while the MIC values of Oxytetracyclin used as the positive control against Bacillus subtilis and Micrococcus luteus were 4.16 µg/mL and 0.40 µg/mL, respectively. While the MIC value of compound C (Figure 13) against Mucor hiemalis (16.66 µg/mL) was the same as that of nystatin used as positive control. The two active metabolites are anthranilic acid derivatives with a phenylethyl core. Since metabolite 340, which contains a phenylmethyl group instead of a phenylethyl residue, was not active, it was concluded that the phenylethyl moiety in compounds 339 and C is essential for their antimicrobial activity [60].
The isolated compound 347, which was obtained in sufficient amounts, was evaluated for antimicrobial activities against S. aureus ATCC25923 and methicillin-resistant S. aureus. Simplicildone A 347 displayed weak antibacterial against Staphylococcus aureus with MIC value of 32 µg/mL. Vancomycin which was used as positive control for bacteria, displayed the MIC values of 0.5 µg/mL and 1.0 µg/mL against both S. aureus and methicillin-resistant S. aureus [63].
The antimicrobial activity of compound 367 was evaluated using the strains of methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus subtilis, and Escherichia coli. Compound 367 exhibited weaker activity in comparison to the positive control tetracycline against methicillin-resistant S. aureus (MRSA) with the MIC value of 128 µg/mL, and against K. pneumoniae and P. aeruginosa with equal MIC values of 32 µg/mL [119].
Compounds 371373 were assayed for their antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli. Compounds 371372 exhibited significant inhibitory activities against B. subtilis and S. aureus with MIC values of 15 µg/mL and 18 µg/mL, respectively. Compound 373 showed moderate inhibitory activities against B. subtilis (MIC 35 µg/mL) and S. aureus (MIC 39 µg/mL). Ampicillin (MIC values: 8 µg/mL, 3.5 µg/mL, 10 µg/mL, 10 µg/mL and 2.5 µg/mL against the 5 bacteria mentioned above) and kanamycin (MIC values: 4 µg/mL, 1.0 µg/mL, 8 µg/mL, 9 µg/mL and 4 µg/mL against the 5 bacteria mentioned above) served as the positive control. In addition, morphological observation showed the rod-shaped cells of B. subtilis growing into long filaments, which reached 1.5- to 2-fold of the length of the original cells after treatment with compounds 371372. The coccoid cells of S. aureus exhibited a similar response and swelled to a 2-fold volume after treatment with compounds 371372 [122].
The antimicrobial activity of the compound 374 was evaluated against the Gram-positive bacteria Staphylococcus aureus (ATCC 25923), methicillin-resistant Staphylococcus aureus (MRSA) (BACHC-MRSA). The resulting inhibition zones were measured in millimeters. 374 displayed antibacterial activity against sensitive and resistant S. aureus, the diameter of inhibition zone was 14 mm, Ampicillin was antibacterial control with the diameter of inhibition zone of 30 mm [123].
Compounds 388 was tested for its antimicrobial activities against Escherichia coli ATCC 25922, Staphyloccocus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, and Mycobacterium Smegmatis MC 2155 ATCC70084. Compound 388 was active against Escherichia coli ATCC 25922 and Staphyloccocus aureus ATCC 25923 with MIC values of 32 µg/mL and 64 µg/mL, respectively. Levofloxacin was used as a positive control with MIC value of 0.12 µg/mL [124].
Fusarithioamide B 389 has been assessed for antibacterial activities towards various microbial strains (Staphylococcus aureus (AUMC No. B-54) and Bacillus cereus (AUMC No. B-5) as Gram-positive bacteria, Escherichia coli (AUMC No. B-53), Pseudomonas aeurginosa (AUMC No. B-73), and Serratia marscescens (AUMC No. B-55) as Gram-negative bacteria) by disc diffusion assay. It possessed high antibacterial potential towards E. coli (Inhibition zone diameter (IZD): 25.1 ± 0.60 mm, MIC value: 3.7 ± 0.08 µg/mL), B. cereus (Inhibition zone diameter (IZD): 23.0 ± 0.36 mm, MIC value: 2.5 ± 0.09 µg/mL), and S. aureus (Inhibition zone diameter (IZD): 17.4 ± 0.09 mm, MIC value: 3.1 ± 0.11 µg/mL) compared to ciprofloxacin used as antibacterial standard (Inhibition zone diameter (IZD): 15.3 ± 0.07 mm, MIC value: 3.4 ± 0.32 µg/mL for S. aureus, Inhibition zone diameter (IZD): 21.2 ± 0.51 mm, MIC value: 2.9 ± 0.20 µg/mL for B. cereus, Inhibition zone diameter (IZD): 25.6 ± 0.22 mm, MIC value: 3.9 ± 0.06 µg/mL for E. coli) [125].
The new compounds were evaluated for their antibacterial activities against five terrestrial pathogenic bacteria, including S. aureus (ATCC 27154), Staphylococcus albus (ATCC 8799), B. cereus (ATCC 11778), Escherichia coli (ATCC 25922), and Micrococcus luteus (ATCC 10240) by the microplate assay method. The result showed that Compounds 392393 showed moderate antibacterial activities against Staphylococcus aureus with the MIC values of 25.0 µg/mL and 12.5 µg/mL, respectively. Ciprofloxacin was used as positive control with the MIC value of 0.39 µg/mL [128].
The MIC of compound 395 against Staphylococcus aureus (MSSA), Methicillin resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae carbapenemase-producing (KPC) was performed. Vochysiamide B 395 displayed considerable antibacterial activity against the Gram-negative bacterium Klebsiella pneumoniae (KPC), a producer of carbapenemases, MIC of 80 μg/mL in comparison with positive controls meropenem and gentamicin with MIC values of 45 μg/mL and 410 μg/mL against KPC [129].
The antimicrobial activities of compounds were tested against six microorganisms by the microdilution method, including Mycobacterium phlei, Bacillus subtilis, Vibrio parahemolyticus, Escherichia coli, Pseudomonas aeruginosa, and Proteus vulgaris. Among them, compound 416 showed promising activity against M. phlei with the same MIC values as positive control ciprofloxacin of 12.5 µM, which indicated the antituberculosis potential. Compound 415 showed activities against B. subtilis with MIC value of 100 µM. Compound 416 showed activities against M. phlei with MIC value of 6.25 µM. Ciprofloxacin was positive control shared same MIC values of 1.56 µM against Mycobacterium phlei and Bacillus subtilis [135].
Compound 418 was tested for antimicrobial activities against two human pathogens (E. coli and S. aureus), seven aquatic bacteria (Aeromonas hydrophila, Edwardsiella tarda, Micrococcus luteus, Pseudomonas aeruginosa, Vibrio alginolyticus, Vibrio harveyi, and Vibrio parahaemolyticus). Compound 418 exhibited inhibitory activity against E. coli, and S. aureus with same MIC values of 32 µg/mL. Positive control was chloramphenicol which with MIC values of 2 µg/mL and 1 µg/mL against E. coli, and S. aureus [136].
Antibacterial activity was evaluated against S. aureus and methicillin-resistant S. aureus. Simplicildone K 430 exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with equal MIC values of 128 μg/mL. Vancomycin was used as a positive control for antibacterial activity and displayed equal MIC values of 0.5 μg/mL against both S. aureus and methicillin-resistant S. aureus [96].

3.1.3. Antiviral Activity

Anti-enterovirus 71 (EV71) was assayed on Vero cells with the CCK-8 (DOjinDo, Kumamoto, Japan) method. The 50% inhibitory concentration (IC50) of the testing compound was calculated using the GraphPad Prism software. Ribavirin was used as the positive control with an IC50 value of 177.0 µM. Vaccinol J 125 exhibited in vitro anti-EV71 with IC50 value of 30.7 µM, and the inhibition effect was stronger than positive control ribavirin [44].
Anti-HIV activities of compound 150 was tested in vitro by HIV-I virus-transfected 293 T cells. At the concentration of 20 μM, 150 showed a weak inhibitory rate of 16.48 ± 6.67%. Efavirenz was used as the positive control, with an inhibitory rate of 88.54 ± 0.45% at the same concentration [47].

3.2. Cytotoxic Activity or Anticancer

Nectrianolins A–C 11, 12, and 13 were evaluated for their in vitro cytotoxicity against HL60 (human leukemia 60) and HeLa cell lines by the MTT method using a published protocol. Compounds 11, 12, and 13 exhibited cytotoxic activity against the HL60 cell line with IC50 values of 1.7 µM, 1.5 µM and 10.1 µM, respectively. Additionally, compounds 11, 12, and 13 exhibited cytotoxicity against the HeLa cell line with IC50 values of 34.7 µM, 16.6 µM and 52.1 µM, respectively [13].
Compounds 29 and 236 were evaluated for their cytotoxic activities against three human tumor cell lines HeLa, HCT116 (Human colon cancer tumor cells), and A549 (Human lung cancer cells), both of them exhibited weak to moderate cytotoxic activities with IC50 values ranging from 21.09 to 55.43 µM (29: 58.75 ± 1.77 µM, 47.75 ± 1.68 µM, 29.58 ± 1.47 µM, 236: 21.18 ± 1.33 µM, 21.04 ± 1.32 µM, 37.33 ± 1.57 µM against HeLa, HCT116 and A549 respectively) [19].
The cytotoxic activity of the isolated compounds 7879 and 113114 were tested against Hela cells. Compound 79 showed weak cytotoxic activities against Hela cells with IC50 value of 43.7 ± 0.43 µM. Compound 78 did not show significant cytotoxic activity. As the oxoindoloditerepene epimers, the 3α-epimer 79 was clearly more cytotoxic than the 3β-epimer 78, suggesting that their cytotoxic activity depended on their stereochemistry. The acetoxy derivatives 113 and 114 showed weak cytotoxic activities against Hela cells with IC50 values of 83.8 ± 5.2 µM and 53.5 ± 2.1 µM respectively [35].
Since many triterpenoids isolated from plants of the family Schisandraceae are reported to reduce the risk of liver diseases and cancer, compounds 93100 were evaluated for in vitro cytotoxicity against human hepaticellular liver carcinoma cell (HepG2), according to the MTT method, with cisplatin as the positive control (IC50 value of 9.8 ± 0.21 µM). Compounds 93100, showed moderate cytotoxic activity with IC50 values ranging from 14.3 to 21.3 µM (IC50 values of compounds 93: 15.6 µM, 94: 16.1 µM, 95: 16.4 µM, 96: 15.4 µM, 97: 17.9 µM, 98: 18.8 µM, 99: 14.3 µM, 100: 21.3 µM). It should be noted that those metabolites 93100 produced during fermentation showed stronger cytotoxicity to HepG2 cell line than that of nigranoic acid, the main component of non-fermented K. angustifolia [39].
The in vitro cytotoxicity of compound 119 against the human acute monocytic leukemia cell line (THP-1) was evaluated using a resazurin-based assay and an ATPlite assay. Compound 119 demonstrated marked cytotoxicity against the human acute monocytic leukemia cell line (THP-1) with the IC50 value of 8.0 µM [42].
The in vitro cytotoxicity assay was performed with some cancer cells including the mouse fibroblast cell line L929, cervix carcinoma cell line KB-3-1, human breast adenocarcinoma MCF-7, human prostate cancer PC-3, squamous carcinoma A431, human lung carcinoma A549 and ovarian carcinoma SKOV-3. Compounds 169, 170 showed significant cytotoxicity against the mouse fibroblast cell line L929 and the cervix carcinoma cell line KB-3-1, with IC50 values ranging from 6.3 to 23 µg/mL (169: 23 µg/mL against the mouse fibroblast cell line L929, 22 µg/mL against cervix carcinoma cell line KB-3-1 170: 6.3 µg/mL against the mouse fibroblast cell line L929, 11 µg/mL against cervix carcinoma cell line KB-3-1). Compound 170 showed the strongest cytotoxicity among the metabolites tested against human breast adenocarcinoma MCF-7 cells with IC50 value of 1.5 µg/mL. Besides, compound 170 showed cytotoxicity against squamous carcinoma A431, human lung carcinoma A549 and ovarian carcinoma SKOV-3 with IC50 values of 6.5 µg/mL, 16 µg/mL and 6.5 µg/mL. Epothilon B was used as positive control (IC50 values against 7 cancer cells mentioned above were 0. 8 ng/mL, 0. 06 ng/mL, 0.04 ng/mL, 1.1 ng/mL, 0.1 ng/mL, 2 ng/mL and 0.12 ng/mL) [52].
Standard MTT assays employing MDA-MB-435 and A549 cell lines were performed. The IC50 was determined by a 50% reduction of the absorbance in the control assay. Compound 176 exhibited cytotoxicity against MDA-MB-435 and A549 cell lines with IC50 values of 16.82 and 20.75 µM, respectively. The positive control was used by Epirubicin (EPI) with IC50 values of 0.26 and 5.60 µM against MDA-MB-435 and A549 cell lines [54].
All isolated new compounds 190194 were evaluated for their cytotoxic activities against various cancer cell lines, which include A549, Raji, HepG2, MCF-7, HL-60 and K562. Compounds 190194 displayed in vitro inhibitory activities against the six tumor cell lines to various degrees. Among them, compound 192 showed the most potent cytotoxicity against all evaluated cell lines with IC50 values of 1.2, 2.0, 1.6, 2.2, 1.0 and 1.2 μg/mL, respectively, which were even stronger than an anti-tumor agent DDP used as positive control (IC50 values against six cell lines: 2.8 μg/mL, 2.1 μg/mL, 2.6 μg/mL, 2.4 μg/mL, 2.1 μg/mL and 2.2 μg/mL). Compounds 193 and 194 also exhibited moderate growth inhibition against six tested cell lines with IC50 6.3–26.8 μg/mL for 193 and IC50 3.1–24.4 μg/mL for 194. However, compounds 190 and 191 were effective only against HL-60 and K562 cell lines (IC50 value: 190: 24.1 μg/mL, 10.7 μg/mL 191: 24.2 μg/mL, 23.1 μg/mL). These results indicated that the keto or hemiketal functionality (e.g., 192195) would play an important role in cytotoxic activity. Additionally, the activity profile reflected that the hydroxyl-substituted position had a different impact on cytotoxic activity. 2-Pyrones were more active as cytotoxic agents if the alkyl chain at C-6 was oxygenated but the addition of the hydroxyl subunit to C-8 and C-9 significantly decreased the activity [59].
The isolated compound 202 was preliminary evaluated for its cytotoxicities against MCF-7, NCI-H460, HepG-2, and SF-268 cell lines with cisplatin as the positive control. The new compound 202 exhibited weak growth inhibitory activity against the tumor cell lines MCF-7 and HepG-2 with IC50 values of 70 and 60 µM, respectively [64].
Cytotoxic activities of compound 209 against HeLa, MCF-7 and A549 cell lines were evaluated by the MTT method. Adriamycin was used as a positive control. The results showed that 209 displayed cytotoxic activity against A549 cell lines with IC50 value of 15.7 μg/mL [66].
Compound 221 was assessed for its antiproliferative activities against the mouse lymphoma (L5178Y) cell line using the in vitro cytotoxicity (MTT) assay and kahalalide F as a standard antiproliferative agent (IC50 = 4.30 µM). Results revealed the new compound, aflaquinolone H (221), exhibited moderate antiproliferative activity (IC50 = 10.3 µM) which highlights the role of the hydroxyl group at C-21 for the antiproliferative activity [71].
Compounds 222223 were evaluated for in vitro inhibition of cell proliferation by the MTT method using a panel of four human cancer cell lines: NCI-H460 (non-small cell lung cancer), SF-268 (CNS glioma), MCF-7 (breast cancer), and PC-3 (prostate adenocarcinoma) cells. Compounds 222 and 223 showed moderate cytotoxicity against four human cancer cell lines with IC50 values of 18.63 ± 1.82, 20.23 ± 2.15, 23.53 ± 2.33 and 20.48 ± 2.04 µM, and 16.47 ± 1.63, 17.57 ± 2.12 20.79 ± 2.39 and 19.43 ± 2.02 µM, respectively, while compound D (Figure 13) was found to be inactive (>50 µM), which suggested -NH2 group might play a very important role for their cytotoxicity. Doxorubicin (Adriamycin) was used as positive control in this assay (IC50 values against the 4 human cancer cell lines: 0.43 ± 0.12 µM, 0.61 ± 0.09 µM, 0.41 ± 0.11 µM and 0.25 ± 0.08 µM respectively) [72].
Compound 241 was also tested for cytotoxicity against SH-SY5Y (human glioma cell lines), HeLa (cervical epithelial cells), HCT116 (human colon cancer cells), HepG2 (human hepatocellular carcinoma cells), A549 (human lung cancer cells), and MCF7 (human breast cancer cells). Compound 241 showed weak cytotoxic effects against HeLa cells with IC50 value of 97.4 μM, while the positive control cisplatin showed IC50 value of 21.1 µM [78].
The cytotoxicity of compound 244 against a human cervical tumor cell line (HeLa) was tested using the MTT assay. Compound 244 presented an IC50 value of 100 μmol/L. Camptothecin was used as positive control and presented an IC50 of 0.12 μmol/L [80].
The cytotoxicities against HBE, THLE, and MDA-MB-231 of compound 252 were evaluated by MTT method. 252 exhibited selective cytotoxicities against MDA-MB-231 with IC50 of 24.6 ±1.3 µg/mL [82].
Compounds 262,426427 were evaluated for their cytotoxicity against a human leukemia cell line (K562), a colon adenocarcinoma cell line (SW480), and a human liver carcinoma cell line (HepG2). Compounds 262 and 427 showed moderate cytotoxic activity against all the tested cell lines with IC50 ranging from 12.0 to 28.3 µM (IC50 values against K562, SW480, and HepG2 cells: 262: 15.9 (13.1–19.3) µM, 12.0 (8.8–16.4) µM, 28.3 (23.2–34.6) µM 427: 20.6 (14.0–30.3) µM, 20.3 (16.8–24.4) µM, 20.4 (16.4–25.4) µM). In addition, compound 426 showed moderate cytotoxicity towards K562 cells with an IC50 value of 18.7 µg/mL. Cisplatin was used as the positive control with IC50 values of 3.8, 5.5, and 6.8 µM toward K562, SW480, and HepG2 cells, respectively [86].
Compound 281 was evaluated cytotoxic activities against three cancer cell lines HCT 116, HeLa, and MCF7, and displayed strong biological effect against MCF7 with halfmaximal inhibitory concentration (IC50) value at 7.73 ± 0.11 µM compared with the cis-platinum (14.32 ± 1.01 µM) [91].
The isolated compound 287 was examined for cytotoxic activity by MTT assay. Camptothecin was used as positive control for HL60 with IC50 = 23.6 nM. 287 exhibited cytotoxicity against human promyelocytic leukemia HL60 cells with IC50 value of 1.33 µM. The higher cytotoxicity of 287 and E (Figure 13) compared to that of the related compounds F (Figure 13) and G (Figure 13) was attributed to their increased cell membrane permeability due to the presence of the hydroxyl group [69].
Compound 288 was investigated for its cytotoxicities against SMMC-7721 cell by MTT method. The results showed that 288 inhibited SMMC-7721 cells proliferation in a dose-dependent manner (100 µM, 50 µM, 25 µM, 12.5 µM, 6.25 µM), with IC50 of 61 + 2.2 µM [31].
The cytotoxicities of compound 297 were tested by using human promyelocytic leukemia HL-60, human hepatoma SMMC-7721, non-small cell lung cancer A-549, breast cancer MCF-7 and human colorectal carcinoma SW4801 cell lines, 297 showed cytotoxicity against MCF-7 with the ratio of inhibition at 72% for a concentration at 40 µM (IC50 of positive control Taxol < 0.008 µM) [98].
The cytotoxicities of compound 311 were evaluated against the A549 and HepG2 cell lines by the MTT method. Newly isolated compound 311 showed weak activities with IC50 values of 11.05 µM and 19.15 µM, respectively, against the tested cell lines. Doxorubicin was used as a reference (0.94 µM and 1.16 µM) [103].
The obtained compound 320 was evaluated for its cytotoxic activities against A549 human lung cancer cells and HepG2 human liver cancer cells. Compound 320 exhibited potent cytotoxic activities towards A549 human lung cancer cells and HepG2 human liver cancer cells with IC50 values of 23.73 ± 3.61 µM and 35.73 ± 2.15 µM, respectively [90].
The anti-tumor activities of compounds 336337 were evaluated against Ramos and H1975 cell lines. 337 displayed the most promising anti-tumor activity against both Ramos and H1975 cell lines with IC50 values of 0.018 µM and 0.252 µM, respectively. Compound 337 may be more effective in anti-tumor activity against Ramos and H1975 than stand drug Ibrutinib and afatinib, with IC50 values of 28.7 µM and 1.97 µM. These findings suggest that compound 337 might be promising lead for leukemia and lung cancer treatments. In addition, 336 also displayed anti-tumor activity against both Ramos and H1975 cell lines with IC50 values of 17.98 and 7.3 µM, respectively [113].
Compound 343 was evaluted for the cytotoxicities against three human tumor cell lines, including a human breast cancer cell line (MDA-MB-435), a human gastric cancer cell line (SGC-7901), and a human lung adenocarcinoma epithelial cell line (A549) by MTT method. It is notable that penochalasin K 343 exhibited remarkable broad-spectrum inhibitory activities against all the tested cell lines (IC50 values against MDA-MB-435, SGC-7901 and A549: 4.65 ± 0.45 µM, 5.32 ± 0.58 µM and 8.73 ± 0.62 µM). Epirubicin was used as a positive control with IC50 values of 0.56 ± 0.06 µM, 0.37 ± 0.11 µM and 0.61 ± 0.05 µM against MDA-MB-435, SGC-7901 and A549 [114].
The cytotoxicity was evaluated by the [3H] thymidine assay using breast cancer (MCF-7) and colon cancer (COLO-205) cell lines. Doxorubicin (10 µg), was used as a positive control with ED50 (50% effective dose) value of 1.8 µg/mL against MCF-7 cell line. Compound 362 showed cytotoxic activity against MCF-7 cell line with ED50 value of >10 µg/mL [116].
Compound 363 was evaluated for its cytototoxicity against different cancer cell lines MOLT-4, A549, MDA-MB-231and MIA PaCa-2 by MTT assay. Interestingly, compound 363 showed considerable cytotoxic potential against the human leukaemia cancer cell line (MOLT-4) with IC50 value of 20 µmol/L, it was not as active as the positive control flavopiridol (IC50 value of 0.2 µmol/L) [117].
Cytotoxicity against four tumor cell lines (A549, HeLa, MCF-7, and THP-1) of compound 365 was evaluated. In the cytotoxic assay, compound 365 displayed weak in vitro cytotoxicity against the THP-1 cell line, with IC50 value of 40.2 µM [118].
The cytotoxic effect of 389 was evaluated in vitro towards ovarian (SK-OV-3), epidermoid (KB), malignantmelanoma (SK-MEL), human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HCT-116), and ductal (BT-549) carcinomas. Doxorubicin (positive control) and DMSO (negative control) were used. It had selective and potent effect towards BT-549, MCF-7, SKOV-3, and HCT-116 cell lines with IC50s 0.09 ± 0.05, 21 ± 0.07, 1.23 ± 0.03, and 0.59 ± 0.01 µM, respectively, compared to doxorubicin (IC50s 0.045 ± 0.11, 0.05 ± 0.01, 0.321 ± 0.21, and 0.24 ± 0.04 µM, respectively). Fusarithioamide B (389) may provide a lead molecule for future developing of antitumor and antimicrobial agents [125].
In the cancer cell line cytoxicity assays, compound 395 displayed low activity against human non-small cell lung A549 and human prostate PC3 cell lines (A549: EC50 (concentration for 50% of maximal effect) = 86.4 μM for 395, PC3: EC50 = 40.25 μM for 395. 1.5 mM hydrogen peroxide was used as positive control (100% dead cells), 0.1% dimethyl sulfoxide was used as negative control (100% live cells) [129].
Compounds 396397 were evaluated for their cytotoxic activity against four human tumor cell lines (SF-268, MCF-7, HepG-2 and A549) by the SRB (Sulforhodamine B) method. As a result, compounds 396, 397 showed weak inhibitory activities against the four tumor cell lines with IC50 values ranging from 30 to 100 µM (IC50 values against SF-268, MCF-7, HepG-2 and A549 396: 41.68 ± 0.88 µM, 37.68 ± 0.3 µM, 48.33 ± 0.1 µM and 53.36 ± 0.91 µM, 397: 69.46 ± 7.08 µM, 97.71 ± 0.72 µM, 79.43 ± 0.63 µM and 0 ≥ 100 µM). Cisplatin was used as a positive control with IC50 values of 3.39 ± 0.29 µM, 3.19 ± 0.12 µM, 2.42 ± 0.14 µM and 1.56 ± 0.08 µM against the four human tumor cell lines [41].
The in vitro cytotoxicity assay was performed according to the MTS method in 96-well microplates. Five human tumor cell lines were used: human myeloid leukemia HL-60, human hepatocellular carcinoma SMMC-7721, lung cancer A-549, breast cancer MCF-7, and human colon cancer SW480, which were obtained from ATCC (Manassas, VA, USA). Cisplatin was used as the positive control for the cancer cell lines (IC50 values against HL-60, A-549, SMMC-7721, MCF-7, and SW480 cell: 4.05 ± 0.11, 19.40 ± 0.71, 14.91 ± 0.36, 22.96 ± 0.58 and 23.15 ± 0.22 μM). Compound 447 demonstrated moderate cytotoxicity against HL-60, A-549, SMMC-7721, MCF-7, and SW480 cell with IC50 values of 15.80, 15.93, 19.42, 19.22, and 23.03 μM, respectively [27].

3.3. Other Activities

α-Glucosidase inhibitors are helpful to prevent deterioration of type 2 diabetes and for the treatment of the disease in the early stage, so the α-glucosidase inhibitory effects of the isolated compounds were evaluated. As a result, compounds 247, 248 exhibited potent α-glucosidase inhibitory activity with IC50 values of 25.8 µM, 54.6 µM, respectively, which were much better than acarbose (IC50 of 703.8 µM) as a positive control. Compounds 7 and 249 showed moderate inhibitory activity against α-glucosidase with IC50 values of 188.7 µM and 178.5 µM, respectively. The results indicated that the configureuration at C-5 in compounds 6 and 7 might affect α-glucosidase inhibitory activity. Moreover, the methoxy group at C-15 in the lasiodiplodin derivatives decreased the activity (248 vs. H (Figure 13)). For compounds 247, I (Figure 13), J (Figure 13), and K (Figure 13), compounds 247 and I showed potent α-glucosidase inhibitory effects, whereas J and K were inactive, which attested that the position of the hydroxyl group had a significant impact on the activity [10].
AChE inhibitory activities of the compound 14 were assayed by the spectrophotometric method. Compound 14 indicated anti-AChE activity with inhibition ratio at 35% in the concentration of 50 μM. Tacrine (Sigma, purity > 99%) was used as a positive control of inhibition ratio at 52.63% with the concentration of 0.333 μM [14].
The inhibition of the marine phytoplankton Chattonella marina, Heterosigma akashiwo, Karlodinium veneficum, and Prorocentrum donghaiense by 3137 were assayed. The results showed that 3234 were more active to C. marina, K. veneficum, and P. donghaiense than 31 and 3537 (IC50 against C. Marina, H. akashiwo, K. veneficum and P. donghaiense: 31: 11, 4.6, 12 and 23 μg/mL 32: 1.2, 4.3, 1.3 and 5.7 μg/mL 33: 3.3, 9.2, 1.5 and 6.8 μg/mL 34: 0.93, 7.8, 2.7 and 4.9 μg/mL 35: 6.7, 2.9, 6.6 and 10 μg/mL 36: 5.4, 5.8, 8.4 and 14 μg/mL 37: 3.7, 6.9, 9.4 and 12 μg/mL). A structure-activity relationship analysis revealed that the phenyl group in 3234 may contribute to their inhibitory ability, but the isomerization at C-9 and/or C-11 of 3237 only has slight influences on their activities. K2Cr2O7 was used as positive control with IC50 values of 0.46, 0.98, 0.89 and 1.9 μg/mL, respectively [21].
The biological effects of compound 38 were evaluated on the seedling growth of Arabidopsis thaliana, and 38 displayed an effect on the root growth but no remarkable inhibition of leaf growth in Arabidopsis thaliana [22].
The antioxidant activity was estimated by using adapted 2, 2′-diphenyl-b-picrylhydrazyl (DPPH) method. Ascorbic acid (IC50 = 2.0 μM) and methanol were used as positive and negative controls, respectively. 49 and 413 showed remarkable antioxidant activity with IC50 values of 2.50 and 5.75 μM respectively [24].
The biological activity properties of compounds 6365 were evaluated for inhibitory activity against pancreatic lipase. Compounds 6365 displayed potent inhibition in the assay with IC50 values of 2.83 ± 0.52, 5.45 ± 0.69, and 6.63 ± 0.89 μM, respectively, compared to the standard kaempferol (1.50 ± 0.21 μM) [29].
Nuclear transcription factor (PXR) can regulate a suite of genes involved in the metabolism, transport, and elimination of their substances, such as CYP3A4 and MRP, therefore, it is regarded as an important target to treat cholestatic liver disorders. So compound 76 was assayed for agonistic effects on PXR. Compound 76 displayed the significant agonistic effect on PXR with EC50 value of 134.91 ± 2.01 nM [33].
Brine shrimp inhibiting assay was assayed. Compound 80 displayed brine shrimp inhibiting activities with IC50 value of 10.1 μmol/mL. The SDS (sodium dodecyl sulfate) was employed as positive control and its inhibiting ratio was 95% for brine shrimp and LC50 0.6 μmol/mL [36].
Monitoring the NO level in LPS-activated cells has become a common approach for evaluating the potential anti-inflammatory activities of compounds. Isolates 8292 were evaluated for their inhibitory activity against NO production in LPS-activated RAW 264.7 marcrophages, while indomethacin was used as a positive control. Compounds 8991 exhibited inhibitory effects with IC50 values of 21, 24 and 16 μM, respectively, which are lower than that of the positive control indomethacin (IC50 = 38 ± 1 μM), while compound 85 exhibited moderate inhibition with an IC50 value of 42 μM. Preliminary structure–activity relationships revealed that the analogues with the S absolute configureuration at C-18 (e.g., 8991) significantly enhanced the activity, as exemplified by compound 89 showing inhibition against NO production in RAW 264.7 marcrophage cells with an IC50 value of 21 μM, whereas compound 87 exerted less than 40% inhibition at 50 μM. In addition, all isolated compounds (8292) were tested for their inhibitory activity of Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB). Compound 89 displayed inhibition with an IC50 value of 19 μM, comparable to the positive control (oleanolic acid, IC50 = 22 ± 1 μM). Compounds 83, 85, 86 and 90 showed moderate inhibitory activity of MptpB with IC50 values of 39 ± 2 μM, 42 ± 3 μM, 28 ± 1 μM and 35 ± 1 μM, respectively [38].
Compounds 135146 were evaluated for their inhibitory effects on the NO production in LPS-stimulated RAW264.7 microglial cells using Griess assay. Meanwhile, the effects of compounds 135146 on cell proliferation/viability were measured using the MTT method. As a result, compounds 138, 139, 142, 143, 145 and 146 exhibited inhibitory activity against NO production with IC50 values in the range of 56.3–98.4 μM (IC50 values of compounds on LPS-stimulated NO production in RAW264.7 macrophage cells 138: 85.2 ± 4.3 µM, 139: 98.4 ± 5.6 µM, 142: 95.9 ± 3.4 µM, 143: 64.8 ± 1.3 µM, 145: 60.0 ± 3.1 µM, 146: 56.3 ± 1.1 µM). Indomethacin was used as a positive control (IC50 = 33.6 ± 1.4 μM) [45].
Measurement of ATP release of thrombin-activated platelets of the isolated compound 168 was investigated by applying D. S. Kim’s method. Compound 168 exhibited inhibitory activities on ATP release of thrombin-activated platelets with IC50 value of 57.6 ± 3.2 μM. Staurosporine served as the positive control with IC50 value of 3.2 ± 0.6 μM [51].
The inhibition of biofilm formation against Staphylococcus aureus DSM 1104 was tested in 96-well tissue microtiter plates. The compounds were tested in concentrations of up to 256 µg/mL. MeOH and cytochalasin B were used as negative and positive control, respectively. Minimum Inhibitory Concentration (MIC) value of 256 µg/mL was observed for metabolite 169 and it showed a weak inhibition of biofilm formation of 20.78% at 256 µg/mL [52].
A colorimetric α-glucosidase (Sigma-Aldrich Co. CAS number: 9001-42-7, E.C 3.2.1.20) assay of compounds 176180 was performed. 1-deoxynojirimycin (St. Louis, MO, USA) was used as a positive control. In addition, The DPPH radical scavenging assay of these compounds was also conducted with 96-well plates using a revised method. The positive control was used by Vitamin C. Compounds 176178 showed significant α-glucosidase inhibitory activity with IC50 values of 35.8 μM, 53.3 μM and 60.2 μM, respectively, compared to 62.8 μM for the positive control (1-deoxynojirimycin). Moreover, compound 179 exhibited radical scavenging activity against DPPH with EC50 value of 68.1 μM, the EC50 value of positive control ascorbic acid was 22.3 μM [54].
The tested compounds 200, 276, 344346 were investigated for their capacity to inhibit biofilm formation in the reference strains of S. aureus, E. faecalis and E. coli. Aacetylquestinol 276, 345 and 200 were found to cause a significant reduction inbiofilm production by E. coli ATCC 25922 with the percentage of biofilm formation: 50.6 ± 17.6%, 23.7 ± 24.8% and 57.6 ± 8.1%, respectively. On the other hand, emodin 344 and 345 showed inhibition of biofilm production in S. aureus ATCC 25923 (21.1 ± 11.5% and 21.8 ± 18.9%). Interestingly, 345, which is the most effective in inhibiting biofilm formation in E. coli ATCC 25922, also caused nearly 80% reduction of the biofilm production in S. aureus ATCC 25923 [62].
Compound 207 was evaluated for its acetylcholinesterase (AChE) inhibitory activity using the Ellman colorimetric method, it showed weak AChE inhibitory activity with the inhibition ratio of 11.9% at the concentration of 50 μmol/mL [65].
The anti-inflammatory activities of the isolated compounds 210211 were evaluated by measuring the inhibitory activity of nitric oxide (NO) production levels in the lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. 210211 exhibited moderate inhibitory activities on NO production in LPS-stimulated RAW264.7 cells without cell cytotoxicities [67].
The transformed products 224225 and the parent compound L (Figure 13) were evaluated for the neuroprotective activity using the LPS-induced neuro-inflammation injury assay. 224225 exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with EC50 values of 35.3 ± 0.9 nM and 32.1 ± 0.9 nM, respectively, while L (EC50 = 8.3 ± 0.4 nM) exhibited comparable activity with the positive control ibuprofen (EC50 = 19.4 ± 0.7 nM). The transformed products 224225 and L all exhibited considerable neuroprotective activity in the invitro LPS-induced neuro-inflammation injury assay, suggesting that the hupA moiety shared by these compounds may be used as a lead structure for the development of neuroprotective drugs [73].
The artificial insect mixed drug method was used to determine the insecticidal activities of compound 228. Compound 228 displayed remarkable insecticidal activities against first instar larvae of the cotton bollworm Helicoverpa armigera with mortality rates of 70.2%. Commercially-available matrine was used as positive control, causing 87.4% mortality rate under the same conditions. Acute cytotoxicity towards hatching rate, malformation and mortality of zebrafish embryos or larvae were also performed. Compounds 227 and 228 significantly decreased the hatching rate of zebrafish embryos, compound 228, used at concentrations of 5–100 μg/L, decreased the hatching rate of zebrafish embryos to below 20% [74].
The potential phytotoxicity of 246 against lettuce seedlings (Lactuca sativa L.) was studied. Aqueous solutions of 246 ranging between 25 and 200 μg mL−1, were assayed for its effects on seed germination, root length, and shoot length of the lettuce. Compound 246 showed the most robust inhibitory effect on root growth. Compound 246 inhibited root growth by 50% at a concentration of 25 µg/mL. In addition, the highest concentration of 246 (200 µg/mL) strongly exerted an inhibitory effect on seed germination (90% inhibition) [81].
Compounds 256257 were investigated for their inhibitory activities against the LPS-activated production of NO in RAW264.7 cells using the Griess assay with indomethacin as a positive control (IC50 = 37.5 ± 1.6 μM). The effects of compounds on cell proliferation/viability were determined using MTT method, and none of the test compounds exhibited cytotoxicity at their effective concentrations. Compounds 256 and 257 showed strong inhibitory effects on the production of NO, with IC50 values of 0.78 ± 0.06 and 1.26 ± 0.11 μM, respectively [84].
In vitro anti-inflammatory effects of compounds 258261 were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. 258261 exhibited excellent inhibitory effects on the production of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) in LPS-induced macrophages with the IC50 values ranging from 16.21 ± 1.62 μM to 35.23 ± 3.32 μM, from 19.83 ± 1.82 μM to 42.57 ± 4.56 μM, from 16.78 ± 1.65 μM to 38.15 ± 3.67 μM, respectively, similar with the positive control indomethacin. Those results indicated that, terrusnolides A–D (258261) might play a significant role as a lead compound in the study of anti-inflammatory agents. In addition, compounds 258261 were also investigated for the inhibitory activities against BACE1 by M-2420 method and acetylcholin esterase (AchE) using Ellman’s method. Compound 260 exhibited weak AchE inhibitory activity with IC50 value of 32.56 ± 3.16 µM, compound 261 exhibited weak BACE1 inhibitory activity with IC50 value of 37.45 ± 4.56 µM. LY2811376 and Donepezil were used as the positive control in BACE1 and AchE inhibitory assay with IC50 values of 0.25 ± 0.04 µM and 0.05 ± 0.01 µM, respectively [85].
The Indoleamine 2,3-dioxygenase (IDO) inhibitory activity assay of compounds 284286 were carried out. The results showed that compound 285 possessed significant inhibitory activity against IDO with IC50 value of 0.11 μM. Epacadostat, as the positive control, was one of the most potent IDO inhibitors with IC50 value of 0.05 μM. For compounds 284 and 286, they showed relatively strong inhibitory activity with IC50 values of 1.47 μM and 6.36 μM, respectively [92].
NF-κB has been considered as an attractive therapeutic target for the cancer research. Compound 288 was investigated for its effects on NF-κB pathway by reporter gene assay. The results showed that it could activate the NF-κB pathway with increments in the relative luciferase activity at a concentration of 50 μM [93].
The phytotoxic activities of 295 and 296 were investigated by seed germination test on lettuce (Lactuca sativa L.) with 2,4-dichlorophenoxyacetic acid (0.3 µg/mL) as the positive control. Compounds 295 and 296 each inhibited the growth of both roots and hypocotyls at 30 µg/mL. Furthermore, 295 suppressed seed germination at 100 µg/mL [97].
Acetylcholinesterase (AChE) inhibitory activities of the compound 302 were assayed by the spectrophotometric method developed by Ellman with modification. 302 showed weak AChE inhibitory activity (The percentage inhibition was at 20%~60% in 50 μM) [99].
The 5-lipoxygenase (5-LOX) inhibitory potential of 306308 from Fusarium sp. was assessed in an attempt to explore their activity against 5-LOX. It is noteworthy that 306 displayed prominent 5-LOX inhibitory activity with IC50 value of 3.61 μM, compared to that of indomethacin (IC50 = 1.17 μM), while 307 and 308 had moderate activity with IC50 values of 7.01 μM and 4.79 μM, respectively [101].
α-Glucosidase inhibitory activity was performed in the 96-well plates and acarbose was used as the positive compound. In the inhibitory assay against α-glucosidase, compound 313 displayed moderate activities [104].
The anti-inflammatory activities of selected isolated 4 compounds 314317 were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Compound 317 showed the most NO inhibitory effects, with the inhibition of 17.4% NO production in LPS stimulated RAW264.7 cells at 10 μM. At the same concentration, compound 315 significantly inhibited the NO production, with 11.2% inhibitory rate. Compound 314 showed weak NO inhibitory effects at 10 μM, with inhibitory rates of 6.5%. At the same concentration, quercetin, the positive control, inhibited NO production to 12.9% [105].
The Superoxide anion radical scavenging activity of compound 331 was investigated. It displayed strong antioxidant activity with EC50 value of 1.08 mg/mL on superoxide anion racdicals. Ascorbic acid (Vc) was used as positive control with EC50 value of 0.33 mg/mL [111].
Compounds 333 and 334 were subjected to motility inhibitory and zoosporicidal activity tests against P. capsici (Phomopsis capsici). Compounds 333 and 334 showed more than 50% motility inhibitory activity (IC50) at a concentration of 50−100 μg/mL [112].
Human carboxylesterases (hCE 1 and hCE 2) are the important enzymes that hydrolyze chemicals with functional groups, such as a carboxylic acid ester and amide, and they are known to play vital roles in drug metabolism and insecticide detoxication. The isolated compounds 379385 were assayed for their inhibitory activities against hCE 2. Loperamide was used as a positive control with IC50 value of 1.31 ± 0.09 µM. Compounds 379, and 383385 displayed significant inhibitory activities against hCE 2 with IC50 values of 10.43 ± 0.51, 6.69 ± 0.85, 12.36 ± 1.27, 18.25 ± 1.78 µM, respectively [94].
The inhibitory effects on human carboxylesterases (hCE1, hCE2) of compound 386 were evaluated. The results demonstrated that bysspectin A 386 was a novel and highly selective inhibitor against hCE2 with the IC50 value of 2.01 µM. Docking simulation also demonstrated that active compound 386 created interaction with the Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2 via hydrogen bonding, revealing its highly selective inhibition toward hCE2 [124].
Compounds 392393 were also evaluated for growth inhibition activity against newly hatched larvae of H. armigera Hubner. Compounds 392 and 393 showed growth inhibition activities against newly hatched larvae of H. armigera Hubner with the IC50 values of 150 and 100 µg/mL, respectively. Azadirachtin was used as positive control with the IC50 value of 25 µg/mL [128].
Antioxidant activity of the compound 403 was determined by DPPH assay and compared with the positive control BHT. Compound 403 showed moderate antioxidant activities with IC50 value of 120.1 ± 11.7 μg/mL [131].
The new compounds 406407 were subjected for determination of the xanthine oxidase (XO) inhibitory activity using microtiter plate based NBT assay. Allopurinol was used as a positive control with IC50 value of 0.18 ± 0.02 µg/mL. 406 and 407 showed XO inhibitory activity with IC50 values of 2.81 ± 0.71 and 0.41 ± 0.1 µg/mL, respectively. The oxidized form of 406 also showed high XO inhibition with IC50 value of 0.35 ± 0.13 µg/mL [133].
Compound 421 was tested for osteoclastic differentiation activity using murine macrophage derived RAW264.7 cells. 421 significantly increased the number of mature osteoclasts at the comparable levels to the positive control of kenpaullone, compared to the negative control (DMSO), suggesting that 421 activated a signaling pathway in osteoclastic differentiation [139].
Phtotoxicity assay against lettuce seedlings of compound 432 was carried out using a published protocol. The new compound (−)-dihydrovertinolide 432 exhibited phytotoxicity against lettuce seedlings at a concentration of 50 mg/L [140].
All new compounds were tested for in vitro anti-inflammatory activities against nitric oxide production in liposaccharide (LPS)-induced RAW264.7 cells, and dexamethasone was used as the positive control. Compound 436 showed significant inhibitory activity against NO production in LPS-induced RAW264.7 cells with an IC50 value of 1.9 μM. They were also evaluated for in vitro antidiabetic activities based on the inhibition of alpha-glucosidase, PTP1b, and XOD. Compounds 437 and 441 showed moderate inhibitory activities toward XOD and PTP1b, respectively, at 10 μM with inhibition rates of 67% and 76% [87].
New compound 447 was tested for acetylcholinesterase (AChE) inhibitory activities using the Ellman method with tacrine as the positive control. The results revealed that compound 447 showed weak AChE inhibitory activity wth IC50 value of 23.85 ± 0.20 μM. Tacrine are the positive control used to estimate AChE inhibitory activity with IC50 value of 0.26 ± 0.02 μM [27].
All information about the new compounds are briefly summarized in the Table 1 below.

4. Conclusions

From 2017–2019, a total of 449 new secondary metabolites isolated from plant endophytic fungi using different culture method like common culture, co-culture with bacteria, addition of metal ions and so on, were summarized in this review. These compounds have a variety of unique structures, the difference in structure leads to various biological activities of these compounds. Some of these metabolites display significant antimicrobial effects, cytotoxic activities, antioxidant activities and other biological activities, which indicate that they have potential to be agents to treat some diseases. In this review, structure-activity relationships of some compounds were also reviewed.
According to genome sequencing, a lot of microorganisms have the potential to produce secondary metabolites with novel structures. However, many fungal gene clusters may be silent under standard laboratory growth conditions. As a result, some pathways to yield secondary metabolites cannot be expressed. Therefore, activating these pathways means that we can get more novel compounds. The approach of microorganism co-culture, involving the cultivation of two or more microorganisms in the same lab environment can do a favour for us. Interestingly, 29 new compounds summarized above were obtained through co-culture of bacteria and fungi or two fungi. Besides, by adding CuCl2 into fermentation medium of an endophytic fungus P. citrinum 46, two compounds were isolated. The results showed that adding Cu2+ into medium to activate silent fungal metabolic pathways can increase the discovery of new compounds.
Because the compounds mentioned above were isolated from endophytic fungi in different parts of different plants in different regions, they have a variety of structures and biological activities. In addition to anti-tumor and anti-microbial activities, some compounds also exhibit unique biological activities. Among them, 7 compounds showed weak to moderate AChE inhibitory activity. Some compounds exhibited moderate to potent α-glucosidase inhibitory activity compared with those of positive control. By using adapted 2,2′-diphenyl-b-picrylhydrazyl (DPPH) method, a few of compounds were found to show moderate to remarkable antioxidant activity. Some of them also showed weak to significant inhibitory activity against NO production in LPS-induced RAW264.7 cells. The biological activity properties of 18 compounds were evaluated for inhibitory activity against some enzymes like pancreatic lipase, the 5-lipoxygenase (5-LOX), the Indoleamine 2,3-dioxygenase (IDO), Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB), the xanthine oxidase (XO) and so on, they showed weak to high inhibition.
Endophytic fungi isolated from different parts of plants are a huge treasure house on account of the discovery of novel secondary metabolites with biological activities and unique structures. Since the endophyte resources were discovered, more and more researches have been conducted on them. Just from my review article, the new secondary metabolites isolated from plant endophytes during the three years from 2017 to 2019 were counted. Among them, 38 articles were published in 2017, 136 new compounds were obtained; 39 articles were published in 2018, 117 new compounds were obtained; 57 articles were published in 2019, and 196 new compounds were obtained. It can be discovered that in the past three years, the research trend of plant endophytes and their metabolites have increased year by year. The more new compounds obtained, the greater the possibility of screening compounds with excellent biological activity. This is also an important significance for researchers to study plant endophytes. Through this review, i hope to arouse more people’s interest and attention in this field and screen out compounds with good biological activities to create a better life for mankind by utilizing endophytes resources.

Author Contributions

C.Z. was responsible for the ideation of the whole article; R.Z. performed the review writing, data collection and data analysis, as well as post-revision work; S.L. contributed to determine the title of the review and made suggestions for the revision of the review; X.Z. helped to revise and proofread the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Elshafie, H.; Viggiani, L.; Mostafa, M.S.; El-Hashash, M.A.; Camele, I.; Bufo, S.A. Biological activity and chemical identification of ornithine lipid produced by Burkholderia gladioli pv. agaricicola ICMP 11096 using LC-MS and NMR analyses. J. Biol. Res.—Bollettino della Società Italiana di Biologia Sperimentale 2018, 90, 96–103. [Google Scholar] [CrossRef]
  2. Camele, I.; Elshafie, H.S.; Caputo, L.; Sakr, S.H.; De Feo, V. Bacillus mojavensis: Biofilm formation and biochemical investigation of its bioactive metabolites. J. Biol. Res.—Bollettino della Società Italiana di Biologia Sperimentale 2019, 92, 39–45. [Google Scholar] [CrossRef]
  3. Kong, D.W.; Niu, R.C.; Mao, Y.Z.; Liu, L.L. Research progress on active metabolites of endophytes. Keshan Branch Heilongjiang Acad. Agric. Sci. 2019, 12, 151–154. [Google Scholar]
  4. Ding, W.J.; Wang, S.S.; Ren, J.Q.; Li, G.; Zhan, J.P. Progress on plant endophyte. Curr. Biotechnol. 2015, 5, 425–428. [Google Scholar]
  5. J in, J.; Zhao, Q.; Zhang, X.M.; Li, W.J. Research progress on bioactive products from endophytes. J. Microbiol. 2018, 38, 103–113. [Google Scholar]
  6. Elshafie, H.; Camele, I.; Sofo, A.; Mazzone, G.; Caivano, M.; Masi, S.; Caniani, D. Mycoremediation effect of Trichoderma harzianum strain T22 combined with ozonation in diesel-contaminated sand. Chemosphere 2020, 252, 126597. [Google Scholar] [CrossRef]
  7. Vogl, A. Mehlund die andiron mehlproduktdercerealien und leguminosen. Nahrunsm Unters Hug Waren 1898, 12, 25–29. [Google Scholar]
  8. Dar, R.A.; Shahnawaz, M.; Qazi, P.H. Fungal Endophytes: An Overview; LAP LAMBERT Academic Publishing: Beau Bassin, Mauritius, 2017; pp. 40–42. [Google Scholar]
  9. Yuan, C.; Ding, G.; Wang, H.-Y.; Guo, Y.-H.; Shang, H.; Ma, X.-J.; Zou, Z.-M. Polyketide-Terpene Hybrid Metabolites from an Endolichenic Fungus Pestalotiopsis sp. BioMed Res. Int. 2017, 2017, 1–10. [Google Scholar] [CrossRef]
  10. Zhang, L.; Niaz, S.I.; Khan, D.; Wang, Z.; Zhu, Y.; Zhou, H.; Lin, Y.; Li, J.; Liu, L. Induction of Diverse Bioactive Secondary Metabolites from the Mangrove Endophytic Fungus Trichoderma sp. (Strain 307) by Co-Cultivation with Acinetobacter johnsonii (Strain B2). Mar. Drugs 2017, 15, 35. [Google Scholar] [CrossRef] [Green Version]
  11. Zhou, P.; Wu, Z.; Tan, D.; Yang, J.; Zhou, Q.; Zeng, F.; Zhang, M.; Bie, Q.; Chen, C.; Xue, Y.; et al. Atrichodermones A–C, three new secondary metabolites from the solid culture of an endophytic fungal strain, Trichoderma atroviride. Fitoterapia 2017, 123, 18–22. [Google Scholar] [CrossRef]
  12. Liu, S.; Dai, H.; Heering, C.; Janiak, C.; Lin, W.; Liu, Z.; Proksch, P. Inducing new secondary metabolites through co-cultivation of the fungus Pestalotiopsis sp. with the bacterium Bacillus subtilis. Tetrahedron Lett. 2017, 58, 257–261. [Google Scholar] [CrossRef]
  13. Ariefta, N.R.; Kristiana, P.; Nurjanto, H.H.; Momma, H.; Kwon, E.; Ashitani, T.; Tawaraya, K.; Murayama, T.; Koseki, T.; Furuno, H.; et al. Nectrianolins A, B, and C, new metabolites produced by endophytic fungus Nectria pseudotrichia 120-1NP. Tetrahedron Lett. 2017, 58, 4082–4086. [Google Scholar] [CrossRef]
  14. Zhou, Q.-Y.; Yang, X.-Q.; Zhang, Z.-X.; Wang, B.-Y.; Hu, M.; Yang, Y.-B.; Zhou, H.; Ding, Z. New azaphilones and tremulane sesquiterpene from endophytic Nigrospora oryzae cocultured with Irpex lacteus. Fitoterapia 2018, 130, 26–30. [Google Scholar] [CrossRef] [PubMed]
  15. Pang, X.-J.; Zhang, S.-B.; Xian, P.-J.; Wu, X.; Yang, D.-F.; Fu, H.; Yang, X.-L. Emericellins A and B: Two sesquiterpenoids with an unprecedented tricyclo[4,4,2,1]hendecane scaffold from the liquid cultures of endophytic fungus Emericella sp. XL 029. Fitoterapia 2018, 131, 55–58. [Google Scholar] [CrossRef]
  16. Yang, H.-X.; Ai, H.-L.; Feng, T.; Wang, W.-X.; Wu, B.; Zheng, Y.; Sun, H.; He, J.; Li, Z.-H.; Liu, J.-K. Trichothecrotocins A–C, Antiphytopathogenic Agents from Potato Endophytic FungusTrichothecium crotocinigenum. Org. Lett. 2018, 20, 8069–8072. [Google Scholar] [CrossRef]
  17. Kong, Z.; Jing, R.; Wu, Y.; Guo, Y.; Geng, Y.; Ji, J.; Qin, L.-P.; Zheng, C.-J. Trichodermadiones A and B from the solid culture of Trichoderma atroviride S361, an endophytic fungus in Cephalotaxus fortunei. Fitoterapia 2018, 127, 362–366. [Google Scholar] [CrossRef]
  18. Wang, P.; Yu, J.-H.; Zhu, K.; Wang, Y.; Jiang, C.-S.; Jiang, C.-S.; Dai, J.-G.; Wu, J.; Zhang, H. Phenolic bisabolane sesquiterpenoids from a Thai mangrove endophytic fungus, Aspergillus sp. xy02. Fitoterapia 2018, 127, 322–327. [Google Scholar] [CrossRef]
  19. Xiao, J.; Lin, L.-B.; Hu, J.-Y.; Duan, D.-Z.; Shi, W.; Zhang, Q.; Han, W.-B.; Wang, L.; Wang, X.-L. Pestalustaines A and B, unprecedented sesquiterpene and coumarin derivatives from endophytic fungus Pestalotiopsis adusta. Tetrahedron Lett. 2018, 59, 1772–1775. [Google Scholar] [CrossRef]
  20. Jiang, C.-X.; Li, J.; Zhang, J.-M.; Jin, X.-J.; Yu, B.; Fang, J.; Wu, Q.-X. Isolation, Identification, and Activity Evaluation of Chemical Constituents from Soil Fungus Fusarium avenaceum SF-1502 and Endophytic Fungus Fusarium proliferatum AF-04. J. Agric. Food Chem. 2019, 67, 1839–1846. [Google Scholar] [CrossRef]
  21. Song, Y.-P.; Miao, F.-P.; Liu, X.-H.; Yin, X.-L.; Ji, N.-Y. Seven chromanoid norbisabolane derivatives from the marine-alga-endophytic fungus Trichoderma asperellum A-YMD-9-2. Fitoter 2019, 135, 107–113. [Google Scholar] [CrossRef]
  22. Tan, X.; Zhang, X.; Yu, M.; Yu, Y.; Guo, Z.; Gong, T.; Niu, S.; Qin, J.; Zou, Z.; Ding, G. Sesquiterpenoids and mycotoxin swainsonine from the locoweed endophytic fungus Alternaria oxytropis. Phytochemistry 2019, 164, 154–161. [Google Scholar] [CrossRef] [PubMed]
  23. Wen, S.; Fan, W.; Guo, H.; Huang, C.; Yan, Z.; Long, Y. Two new secondary metabolites from the mangrove endophytic fungus Pleosporales sp. SK7. Nat. Prod. Res. 2020, 34, 2919–2925. [Google Scholar] [CrossRef] [PubMed]
  24. Duan, X.; Qin, D.; Song, H.C.; Gao, T.; Zuo, S.; Yan, X.; Wang, J.-Q.; Ding, X.; Di, Y.-T.; Dong, J. Irpexlacte A-D, four new bioactive metabolites of endophytic fungus Irpex lacteus DR10-1 from the waterlogging tolerant plant Distylium chinense. Phytochemistry Lett. 2019, 32, 151–156. [Google Scholar] [CrossRef]
  25. Shi, X.-S.; Meng, L.-H.; Li, X.-M.; Li, X.; Wang, D.-J.; Li, H.-L.; Zhou, X.-W.; Wang, B.-G. Trichocadinins B–G: Antimicrobial Cadinane Sesquiterpenes from Trichoderma virens QA-8, an Endophytic Fungus Obtained from the Medicinal Plant Artemisia argyi. J. Nat. Prod. 2019, 82, 2470–2476. [Google Scholar] [CrossRef] [PubMed]
  26. Xu, J.; Hu, Y.-W.; Qu, W.; Chen, M.-H.; Zhou, L.-S.; Bi, Q.-R.; Luo, J.-G.; Liu, W.-Y.; Feng, F.; Zhang, J. Cytotoxic and neuroprotective activities of constituents from Alternaria alternate, a fungal endophyte of Psidium littorale. Bioorganic Chem. 2019, 90, 103046. [Google Scholar] [CrossRef]
  27. Li, H.T.; Tang, L.H.; Liu, T.; Yang, R.N.; Yang, Y.B.; Zhou, H.; Ding, Z.T. Protoilludane-type sesquiterpenoids from Armillaria sp. by co-culture with the endophytic fungus Epicoccum sp. associated with Gastrodia elata. Bioorg. Chem. 2019, 95, 103503. [Google Scholar] [CrossRef]
  28. Kemda, P.N.; Akone, S.H.; Tontsa, A.T.; Zhen, L.; Muller, W.E.; Proksch, P.; Nkengfack, A.E. Colletotrin: A sesquiterpene lactone from the endophytic fungus Colletotrichum gloeosporioides associated with Trichilia monadelpha. Zeitschrift für Naturforschung B 2017, 72, 697–703. [Google Scholar] [CrossRef]
  29. Wang, Y.-N.; Xia, G.-Y.; Wang, L.-Y.; Ge, G.; Zhang, H.-W.; Zhang, J.-F.; Wu, Y.-Z.; Lin, S. Purpurolide A, 5/5/5 Spirocyclic Sesquiterpene Lactone in Nature from the Endophytic Fungus Penicillium purpurogenum. Org. Lett. 2018, 20, 7341–7344. [Google Scholar] [CrossRef]
  30. Chen, J.; Bai, X.; Hua, Y.; Zhang, H.; Wang, H. Fusariumins C and D, two novel antimicrobial agents from Fusarium oxysporum ZZP-R1 symbiotic on Rumex madaio Makino. Fitoterapia 2019, 134, 1–4. [Google Scholar] [CrossRef]
  31. Ariefta, N.R.; Kristiana, P.; Aboshi, T.; Murayama, T.; Tawaraya, K.; Koseki, T.; Kurisawa, N.; Kimura, K.-I.; Shiono, Y. New isocoumarins, naphthoquinones, and a cleistanthane-type diterpene from Nectria pseudotrichia 120-1NP. Fitoterapia 2018, 127, 356–361. [Google Scholar] [CrossRef]
  32. Zhao, J.-C.; Wang, Y.-L.; Zhang, T.-Y.; Chen, Z.-J.; Yang, T.-M.; Wu, Y.-Y.; Sun, C.-P.; Ma, X.-C.; Zhang, Y.-X. Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents. Phytochemistry 2018, 148, 21–28. [Google Scholar] [CrossRef] [PubMed]
  33. Zhao, J.-C.; Luan, Z.-L.; Liang, J.-H.; Cheng, Z.-B.; Sun, C.-P.; Wang, Y.-L.; Zhang, M.-Y.; Zhang, T.-Y.; Wang, Y.; Yang, T.-M.; et al. Drechmerin H, a novel 1(2), 2(18)-diseco indole diterpenoid from the fungus Drechmeria sp. as a natural agonist of human pregnane X receptor. Bioorganic Chem. 2018, 79, 250–256. [Google Scholar] [CrossRef] [PubMed]
  34. Bang, S.; Song, J.H.; Lee, D.; Lee, C.; Kim, S.; Kang, K.S.; Lee, J.; Shim, S.H. Neuroprotective Secondary Metabolite Produced by an Endophytic Fungus, Neosartorya fischeri JS0553, Isolated from Glehnia littoralis. J. Agric. Food Chem. 2019, 67, 1831–1838. [Google Scholar] [CrossRef] [PubMed]
  35. Elsbaey, M.; Tanaka, C.; Miyamoto, T. New secondary metabolites from the mangrove endophytic fungus Aspergillus versicolor. Phytochem. Lett. 2019, 32, 70–76. [Google Scholar] [CrossRef]
  36. Bao, S.-S.; Liu, H.-H.; Zhang, X.-Q.; Liu, C.-X.; Li, X.-C.; Guo, Z.-Y. Xylaroisopimaranin A, a New Isopimarane Derivative from an Endophytic Fungus Xylaralyce sp. Nat. Prod. Sci. 2019, 25, 228–232. [Google Scholar] [CrossRef]
  37. Wang, H.; Umeokoli, B.O.; Eze, P.M.; Heering, C.; Janiak, C.; Müller, W.E.; Orfali, R.S.; Hartmann, R.; Dai, H.; Lin, W.; et al. Secondary metabolites of the lichen-associated fungus Apiospora montagnei. Tetrahedron Lett. 2017, 58, 1702–1705. [Google Scholar] [CrossRef]
  38. Cai, R.; Jiang, H.; Mo, Y.; Guo, H.; Li, C.; Long, Y.; Zang, Z.; She, Z. Ophiobolin-Type Sesterterpenoids from the Mangrove Endophytic Fungus Aspergillus sp. ZJ-68. J. Nat. Prod. 2019, 82, 2268–2278. [Google Scholar] [CrossRef]
  39. Qin, D.; Shen, W.; Wang, J.-Q.; Han, M.; Chai, F.; Duan, X.; Yan, X.; Guo, J.; Gao, T.; Zuo, S.; et al. Enhanced production of unusual triterpenoids from Kadsura angustifolia fermented by a symbiont endophytic fungus, Penicillium sp. SWUKD4.1850. Phytochemistry 2019, 158, 56–66. [Google Scholar] [CrossRef]
  40. Ma, K.-L.; Wei, W.-J.; Li, H.-Y.; Song, Q.-Y.; Dong, S.-H.; Gao, K. Meroterpenoids with diverse ring systems and dioxolanone-type secondary metabolites from Phyllosticta capitalensis and their phytotoxic activity. Tetrahedron 2019, 75, 4611–4619. [Google Scholar] [CrossRef]
  41. Liu, H.; Chen, Y.; Li, H.; Li, S.; Tan, H.; Liu, Z.; Li, D.; Liu, H.; Zhang, W. Four new metabolites from the endophytic fungus Diaporthe lithocarpus A740. Fitoterapia 2019, 137, 104260. [Google Scholar] [CrossRef]
  42. Li, G.; Kusari, S.; Golz, C.; Laatsch, H.; Strohmann, C.; Spiteller, M. Epigenetic Modulation of Endophytic Eupenicillium sp. LG41 by a Histone Deacetylase Inhibitor for Production of Decalin-Containing Compounds. J. Nat. Prod. 2017, 80, 983–988. [Google Scholar] [CrossRef] [PubMed]
  43. Tang, J.-W.; Wang, W.-G.; Li, A.; Yan, B.-C.; Chen, R.; Li, X.-N.; Du, X.; Sun, H.-D.; Pu, J.-X. Polyketides from the endophytic fungus Phomopsis sp. sh917 by using the one strain/many compounds strategy. Tetrahedron 2017, 73, 3577–3584. [Google Scholar] [CrossRef]
  44. Wang, J.; Liang, R.; Liao, S.-R.; Yang, B.; Tu, Z.-C.; Lin, X.-P.; Wang, B.-G.; Liu, Y. Vaccinols J–S, ten new salicyloid derivatives from the marine mangrove-derived endophytic fungus Pestalotiopsis vaccinii. Fitoterapia 2017, 120, 164–170. [Google Scholar] [CrossRef] [PubMed]
  45. Qi, B.; Liu, X.; Mo, T.; Li, S.-S.; Wang, J.; Shi, X.-P.; Wang, X.-H.; Zhu, Z.-X.; Zhao, Y.-F.; Jin, H.-W.; et al. Nitric oxide inhibitory polyketides from Penicillium chrysogenum MT-12, an endophytic fungus isolated from Huperzia serrata. Fitoterapia 2017, 123, 35–43. [Google Scholar] [CrossRef]
  46. Kamdem, R.S.; Pascal, W.; Rehberg, N.; Van Geelen, L.; Höfert, S.-P.; Knedel, T.; Janiak, C.; Sureechatchaiyan, P.; Kassack, M.U.; Lin, W.; et al. Metabolites from the endophytic fungus Cylindrocarpon sp. isolated from tropical plant Sapium ellipticum. Fitoterapia 2018, 128, 175–179. [Google Scholar] [CrossRef]
  47. Hu, H.-B.; Luo, Y.-F.; Wang, P.; Wang, W.-J.; Wu, J. Xanthone-derived polyketides from the Thai mangrove endophytic fungus Phomopsis sp. xy21. Fitoterapia 2018, 131, 265–271. [Google Scholar] [CrossRef]
  48. Tawfike, A.F.; Romli, M.; Clements, C.; Abbott, G.; Young, L.; Schumacher, M.; Diederich, M.; Farag, M.; Edrada-Ebel, R. Isolation of anticancer and anti-trypanosome secondary metabolites from the endophytic fungus Aspergillus flocculus via bioactivity guided isolation and MS based metabolomics. J. Chromatogr. B 2019, 71–83. [Google Scholar] [CrossRef] [Green Version]
  49. Luo, Y.-P.; Zheng, C.-J.; Chen, G.-Y.; Song, X.-P.; Wang, Z. Three new polyketides from a mangrove-derived fungus Colletotrichum gloeosporioides. J. Antibiot. 2019, 72, 513–517. [Google Scholar] [CrossRef]
  50. Suzuki, T.; Ariefta, N.R.; Koseki, T.; Furuno, H.; Kwon, E.; Momma, H.; Harneti, D.; Maharani, R.; Supratman, U.; Kimura, K.-I.; et al. New polyketides, paralactonic acids A–E produced by Paraconiothyrium sp. SW-B-1, an endophytic fungus associated with a seaweed, Chondrus ocellatus Holmes. Fitoterapia 2019, 132, 75–81. [Google Scholar] [CrossRef]
  51. Yang, H.; Qi, B.; Ding, N.; Jiang, F.; Jia, F.; Luo, Y.; Xu, X.; Wang, L.; Zhu, Z.; Liu, X.; et al. Polyketides from Alternaria alternata MT-47, an endophytic fungus isolated from Huperzia serrata. Fitoterapia 2019, 137, 104282. [Google Scholar] [CrossRef]
  52. Narmani, A.; Teponno, R.B.; Helaly, S.E.; Arzanlou, M.; Stadler, M. Cytotoxic, anti-biofilm and antimicrobial polyketides from the plant associated fungus Chaetosphaeronema achilleae. Fitoterapia 2019, 139, 104390. [Google Scholar] [CrossRef] [PubMed]
  53. Neuhaus, G.F.; Adpressa, D.A.; Bruhn, T.; Loesgen, S. Polyketides from Marine-Derived Aspergillus porosus: Challenges and Opportunities for Determining Absolute Configuration. J. Nat. Prod. 2019, 82, 2780–2789. [Google Scholar] [CrossRef] [PubMed]
  54. Chen, Y.; Yang, W.; Zou, G.; Chen, S.; Pang, J.; She, Z. Bioactive polyketides from the mangrove endophytic fungi Phoma sp. SYSU-SK-7. Fitoterapia 2019, 139, 104369. [Google Scholar] [CrossRef] [PubMed]
  55. Yu, H.; Höfert, S.-P.; Moussa, M.; Janiak, C.; Müller, W.E.; Umeokoli, B.O.; Dai, H.; Liu, Z.; Proksch, P. Polyketides and nitrogenous metabolites from the endophytic fungus Phomopsis sp. D15a2a. Tetrahedron Lett. 2019, 60, 151325. [Google Scholar] [CrossRef]
  56. Xia, G.Y.; Wang, L.Y.; Xia, H.; Wu, Y.Z.; Wang, Y.N.; Lin, P.C.; Lin, S. Three new polyketides from the endophytic fungus Penicillium purpurogenum. J. Asian Nat. Prod. Res. 2019, 22, 233–240. [Google Scholar] [CrossRef] [PubMed]
  57. Li, C.; Sarotti, A.M.; Yang, B.; Turkson, J.; Cao, S. A New N-methoxypyridone from the Co-Cultivation of Hawaiian Endophytic Fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062. Molecules 2017, 22, 1166. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  58. McMullin, D.R.; Green, B.D.; Prince, N.C.; Tanney, J.B.; Miller, J.D. Natural Products ofPiceaEndophytes from the Acadian Forest. J. Nat. Prod. 2017, 80, 1475–1483. [Google Scholar] [CrossRef]
  59. Song, H.-C.; Qin, D.; Han, M.-J.; Wang, L.; Zhang, K.; Dong, J.-Y. Bioactive 2-pyrone metabolites from an endophytic Phomopsis asparagi SWUKJ5.2020 of Kadsura angustifolia. Phytochem. Lett. 2017, 22, 235–240. [Google Scholar] [CrossRef]
  60. Teponno, R.B.; Noumeur, S.R.; Helaly, S.E.; Hüttel, S.; Harzallah, D.; Stadler, M. Furanones and Anthranilic Acid Derivatives from the Endophytic Fungus Dendrothyrium variisporum. Molecules 2017, 22, 1674. [Google Scholar] [CrossRef] [Green Version]
  61. Wang, Y.; Liu, H.; Chen, Y.; Sun, Z.-H.; Li, H.-H.; Li, S.; Yan, M.; Zhang, W. Two New Metabolites from the Endophytic Fungus Alternaria sp. A744 Derived from Morinda officinalis. Molecules 2017, 22, 765. [Google Scholar] [CrossRef] [Green Version]
  62. Zin, W.W.M.; Buttachon, S.; Dethoup, T.; Pereira, J.A.; Gales, L.; Inácio, Â.S.; Da Costa, P.M.; Lee, M.; Sekeroglu, N.; Silva, A.M.S.; et al. Antibacterial and antibiofilm activities of the metabolites isolated from the culture of the mangrove-derived endophytic fungus Eurotium chevalieri KUFA 0006. Phytochemistry 2017, 141, 86–97. [Google Scholar] [CrossRef] [PubMed]
  63. Saetang, P.; Rukachaisirikul, V.; Phongpaichit, S.; Preedanon, S.; Sakayaroj, J.; Borwornpinyo, S.; Seemakhan, S.; Muanprasat, C. Depsidones and an α-pyrone derivative from Simpilcillium sp. PSU-H41, an endophytic fungus from Hevea brasiliensis leaf. Phytochemistry 2017, 143, 115–123. [Google Scholar] [CrossRef]
  64. Liu, H.; Tan, H.; Liu, Y.; Chen, Y.; Li, S.; Sun, Z.-H.; Li, H.; Qiu, S.-X.; Zhang, W.-M. Three new highly-oxygenated metabolites from the endophytic fungus Cytospora rhizophorae A761. Fitoterapia 2017, 117, 1–5. [Google Scholar] [CrossRef] [PubMed]
  65. Xiao, W.-J.; Chen, H.-Q.; Wang, H.; Cai, C.; Mei, W.-L.; Dai, H.-F. New secondary metabolites from the endophytic fungus Fusarium sp. HP-2 isolated from “Qi-Nan” agarwood. Fitoterapia 2018, 130, 180–183. [Google Scholar] [CrossRef] [PubMed]
  66. Zheng, C.-J.; Liao, H.-X.; Mei, R.-Q.; Huang, G.-L.; Yang, L.-J.; Zhou, X.-M.; Shao, T.-M.; Chen, G.-Y.; Wang, C.-Y. Two new benzophenones and one new natural amide alkaloid isolated from a mangrove-derived Fungus Penicillium citrinum. Nat. Prod. Res. 2018, 33, 1127–1134. [Google Scholar] [CrossRef]
  67. Kim, J.W.; Choi, H.G.; Song, J.H.; Kang, K.S.; Shim, S.H. Bioactive secondary metabolites from an endophytic fungus Phoma sp. PF2 derived from Artemisia princeps Pamp. J. Antibiot. 2019, 72, 174–177. [Google Scholar] [CrossRef]
  68. Kamel, R.A.; Abdel-Razek, A.S.; Hamed, A.; Ibrahim, R.R.; Stammler, H.-G.; Frese, M.; Sewald, N.; Shaaban, M. Isoshamixanthone: A new pyrano xanthone from endophytic Aspergillus sp. ASCLA and absolute configuration of epiisoshamixanthone. Nat. Prod. Res. 2019, 34, 1080–1090. [Google Scholar] [CrossRef]
  69. Yan, W.; Cao, L.-L.; Zhang, Y.-Y.; Zhao, R.; Zhao, S.-S.; Khan, B.; Ye, Y. New Metabolites from Endophytic Fungus Chaetomium globosum CDW7. Molecules 2018, 23, 2873. [Google Scholar] [CrossRef] [Green Version]
  70. Kamdem, R.S.; Wang, H.; Wafo, P.; Ebrahim, W.; Özkaya, F.C.; Makhloufi, G.; Janiak, C.; Sureechatchaiyan, P.; Kassack, M.U.; Lin, W.; et al. Induction of new metabolites from the endophytic fungus Bionectria sp. through bacterial co-culture. Fitoterapia 2018, 124, 132–136. [Google Scholar] [CrossRef]
  71. Ebada, S.S.; El-Neketi, M.; Ebrahim, W.; Mándi, A.; Kurtán, T.; Kalscheuer, R.; Müller, W.E.G.; Proksch, P. Cytotoxic secondary metabolites from the endophytic fungus Aspergillus versicolor KU258497. Phytochem. Lett. 2018, 24, 88–93. [Google Scholar] [CrossRef]
  72. Rao, L.; You, Y.-X.; Su, Y.; Liu, Y.; He, Q.; Fan, Y.; Hu, F.; Xu, Y.-K.; Zhang, C.-R. Two spiroketal derivatives with an unprecedented amino group and their cytotoxicity evaluation from the endophytic fungus Pestalotiopsis flavidula. Fitoterapia 2019, 135, 5–8. [Google Scholar] [CrossRef] [PubMed]
  73. Ying, Y.-M.; Xu, Y.-L.; Yu, H.-F.; Zhang, C.-X.; Mao, W.; Tong, C.-P.; Zhang, Z.-D.; Tang, Q.-Y.; Zhang, Y.; Shan, W.-G.; et al. Biotransformation of Huperzine A by Irpex lacteus-A fungal endophyte of Huperzia serrata. Fitoterapia 2019, 138, 104341. [Google Scholar] [CrossRef] [PubMed]
  74. Zhang, P.; Yuan, X.-L.; Du, Y.-M.; Zhang, H.-B.; Shen, G.-M.; Zhang, Z.-F.; Liang, Y.-J.; Zhao, D.-L.; Xu, K. Angularly Prenylated Indole Alkaloids with Antimicrobial and Insecticidal Activities from an Endophytic Fungus Fusarium sambucinum TE-6L. J. Agric. Food Chem. 2019, 67, 11994–12001. [Google Scholar] [CrossRef] [PubMed]
  75. Xu, Z.; Wu, X.; Li, G.; Feng, Z.; Xu, J. Pestalotiopisorin B, a new isocoumarin derivative from the mangrove endophytic fungus Pestalotiopsis sp. HHL101. Nat. Prod. Res. 2019, 34, 1002–1007. [Google Scholar] [CrossRef] [PubMed]
  76. Ding, Z.; Tao, T.; Wang, L.; Zhao, Y.; Huang, H.; Zhang, D.; Liu, M.; Wang, Z.; Han, J. Bioprospecting of Novel and Bioactive Metabolites from Endophytic Fungi Isolated from Rubber Tree Ficus elastica Leaves. J. Microbiol. Biotechnol. 2019, 29, 731–738. [Google Scholar] [CrossRef] [Green Version]
  77. Cao, J.; Li, X.-M.; Li, X.; Li, H.-L.; Meng, L.-H.; Wang, B.-G. New lactone and isocoumarin derivatives from the marine mangrove-derived endophytic fungus Penicillium coffeae MA-314. Phytochem. Lett. 2019, 32, 1–5. [Google Scholar] [CrossRef]
  78. Guo, L.; Niu, S.; Chen, S.; Liu, L. Diaporone A, a new antibacterial secondary metabolite from the plant endophytic fungus Diaporthe sp. J. Antibiot. 2019, 73, 116–119. [Google Scholar] [CrossRef]
  79. Orfali, R.S.; Ebrahim, W.; El-Shafae, A.M. Secondary Metabolites from Alternaria sp., a Fungal Endophyte Isolated from the Seeds of Ziziphus jujuba. Chem. Nat. Compd. 2017, 53, 1031–1034. [Google Scholar] [CrossRef]
  80. Silva, G.H.; Zeraik, M.L.; De Oliveira, C.M.; Teles, H.L.; Trevisan, H.C.; Pfenning, L.H.; Nicolli, C.P.; Young, M.C.M.; Mascarenhas, Y.P.; Abreu, L.M.; et al. Lactone Derivatives Produced by a Phaeoacremonium sp., an Endophytic Fungus from Senna spectabilis. J. Nat. Prod. 2017, 80, 1674–1678. [Google Scholar] [CrossRef] [Green Version]
  81. Tchoukoua, A.; Ota, T.; Akanuma, R.; Ju, Y.-M.; Supratman, U.; Murayama, T.; Koseki, T.; Shiono, Y. A phytotoxic bicyclic lactone and other compounds from endophyte Xylaria curta. Nat. Prod. Res. 2017, 31, 2113–2118. [Google Scholar] [CrossRef]
  82. Yuan, W.-H.; Teng, M.-T.; Sun, S.-S.; Ma, L.; Yuan, B.; Ren, Q.; Zhang, P. Active Metabolites from Endolichenic FungusTalaromycessp. Chem. Biodivers. 2018, 15, e1800371. [Google Scholar] [CrossRef] [PubMed]
  83. Yang, Y.-H.; Yang, D.-S.; Li, G.-H.; Liu, R.; Huang, X.; Zhang, K.-Q.; Zhao, P.-J. New secondary metabolites from an engineering mutant of endophytic Streptomyces sp. CS. Fitoterapia 2018, 130, 17–25. [Google Scholar] [CrossRef] [PubMed]
  84. Liao, G.; Wu, P.; Xue, J.; Liu, L.; Li, H.; Wei, X. Asperimides A–D, anti-inflammatory aromatic butenolides from a tropical endophytic fungus Aspergillus terreus. Fitoterapia 2018, 131, 50–54. [Google Scholar] [CrossRef] [PubMed]
  85. Qi, C.; Gao, W.; Wang, J.; Liu, M.; Zhang, Y.; Chen, C.; Hu, Z.; Xue, Y.; Li, D.; Zhang, Q.; et al. Terrusnolides A-D, new butenolides with anti-inflammatory activities from an endophytic Aspergillus from Tripterygium wilfordii. Fitoterapia 2018, 130, 134–139. [Google Scholar] [CrossRef] [PubMed]
  86. Basnet, B.B.; Chen, B.; Suleimen, Y.M.; Ma, K.; Guo, S.; Bao, L.; Huang, Y.; Liu, H. Cytotoxic Secondary Metabolites from the Endolichenic Fungus Hypoxylon fuscum. Planta Medica 2019, 85, 1088–1097. [Google Scholar] [CrossRef] [PubMed]
  87. Zhao, J.-Y.; Wang, X.-J.; Liu, Z.; Meng, F.-X.; Sun, S.-F.; Ye, F.; Liu, Y.-B. Nonadride and Spirocyclic Anhydride Derivatives from the Plant Endophytic Fungus Talaromyces purpurogenus. J. Nat. Prod. 2019, 82, 2953–2962. [Google Scholar] [CrossRef]
  88. Yang, H.-G.; Li, J.-J.; Chen, S.-M.; Mou, L.-M.; Zou, J.; Wang, C.-X.; Chen, G.; Qin, S.-Y.; Yao, X.-S.; Gao, H. Phenylisotertronic acids from the TCM endophytic fungus Phyllosticta sp. Fitoterapia 2018, 124, 86–91. [Google Scholar] [CrossRef]
  89. Rathnayake, G.R.N.; Kumar, N.S.; Jayasinghe, L.; Araya, H.; Fujimoto, Y. Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis microspora. Nat. Prod. Bioprospecting 2019, 9, 411–417. [Google Scholar] [CrossRef] [Green Version]
  90. Hu, Y.; Zhang, J.; Liu, D.; Guo, J.; Liu, T.; Xin, Z. Pencitrin and pencitrinol, two new citrinin derivatives from an endophytic fungus Penicillium citrinum salicorn 46. Phytochem. Lett. 2017, 22, 229–234. [Google Scholar] [CrossRef]
  91. Tan, X.-M.; Li, L.-Y.; Sun, L.-Y.; Sun, B.-D.; Niu, S.-B.; Wang, M.-H.; Zhang, X.-Y.; Sun, W.-S.; Zhang, G.-S.; Deng, H.; et al. Spiciferone analogs from an endophytic fungus Phoma betae collected from desert plants in West China. J. Antibiot. 2018, 71, 613–617. [Google Scholar] [CrossRef]
  92. Cui, H.; Zhang, H.; Liu, Y.; Gu, Q.; Xu, J.; Huang, X.; She, Z. Ethylnaphthoquinone derivatives as inhibitors of indoleamine-2, 3-dioxygenase from the mangrove endophytic fungus Neofusicoccum austral SYSU-SKS024. Fitoterapia 2018, 125, 281–285. [Google Scholar] [CrossRef] [PubMed]
  93. Tian, W.; Liao, Z.; Zhou, M.; Wang, G.; Wu, Y.; Gao, S.; Qiu, D.; Liu, X.; Lin, T.-; Chen, H. Cytoskyrin C, an unusual asymmetric bisanthraquinone with cage-like skeleton from the endophytic fungus Diaporthe sp. Fitoterapia 2018, 128, 253–257. [Google Scholar] [CrossRef] [PubMed]
  94. Zhang, J.; Liang, J.-H.; Zhao, J.-C.; Wang, Y.-L.; Dong, P.-P.; Liu, X.-G.; Zhang, T.-Y.; Wu, Y.-Y.; Shang, D.; Zhang, Y.-X.; et al. Xylarianins A-D from the endophytic fungus Xylaria sp. SYPF 8246 as natural inhibitors of human carboxylesterase 2. Bioorganic Chem. 2018, 81, 350–355. [Google Scholar] [CrossRef] [PubMed]
  95. Padhi, S.; Masi, M.; Cimmino, A.; Tuzi, A.; Jena, S.; Tayung, K.; Evidente, A. Funiculosone, a substituted dihydroxanthene-1,9-dione with two of its analogues produced by an endolichenic fungus Talaromyces funiculosus and their antimicrobial activity. Phytochemistry 2019, 157, 175–183. [Google Scholar] [CrossRef] [PubMed]
  96. Rukachaisirikul, V.; Chinpha, S.; Saetang, P.; Phongpaichit, S.; Jungsuttiwong, S.; Hadsadee, S.; Sakayaroj, J.; Preedanon, S.; Temkitthawon, P.; Ingkaninan, K. Depsidones and a dihydroxanthenone from the endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261. Fitoterapia 2019, 138, 104286. [Google Scholar] [CrossRef]
  97. Supratman, U.; Hirai, N.; Sato, S.; Watanabe, K.; Malik, A.; Annas, S.; Harneti, D.; Maharani, R.; Koseki, T.; Shiono, Y. New naphthoquinone derivatives from Fusarium napiforme of a mangrove plant. Nat. Prod. Res. 2019, 1–7. [Google Scholar] [CrossRef] [PubMed]
  98. Li, W.; Yang, X.-Q.; Yang, Y.-B.; Zhao, L.-X.; Zhou, Q.-Y.; Zhang, Z.-X.; Zhou, H.; Hu, M.; Ruan, B.-H.; Ding, Z.-T. A Novel Steroid Derivative and a New Steroidal Saponin from Endophytic Fungus Xylaria sp. Nat. Prod. Commun. 2017, 12, 901–904. [Google Scholar] [CrossRef] [Green Version]
  99. Yu, F.-X.; Li, Z.; Chen, Y.; Yang, Y.-H.; Li, G.-H.; Zhao, P.-J. Four new steroids from the endophytic fungus Chaetomium sp. M453 derived of Chinese herbal medicine Huperzia serrata. Fitoterapia 2017, 117, 41–46. [Google Scholar] [CrossRef]
  100. Huang, R.-L.; Zheng, C.-J.; Zhou, X.-M.; Song, X.-M.; Wu, P.-P.; Zhao, Y.-F.; Chen, G.-Y.; Song, X.-P.; Han, C.-R. Three new methylated Δ8-pregnene steroids from the Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2. Bioorganic Chem. 2020, 95, 102927. [Google Scholar] [CrossRef]
  101. Khayat, M.T.; Ibrahim, S.R.M.; Mohamed, G.A.A.; Abdallah, H.M. Anti-inflammatory metabolites from endophytic fungus Fusarium sp. Phytochem. Lett. 2019, 29, 104–109. [Google Scholar] [CrossRef]
  102. Wang, Z.-R.; Li, G.; Ji, L.-X.; Wang, H.-H.; Gao, H.; Peng, X.-P.; Lou, H.-X. Induced production of steroids by co-cultivation of two endophytes from Mahonia fortunei. Steroids 2019, 145, 1–4. [Google Scholar] [CrossRef] [PubMed]
  103. Yu, S.; Zhu, Y.-X.; Peng, C.; Li, J. Two new sterol derivatives isolated from the endophytic fungus Aspergillus tubingensis YP-2. Nat. Prod. Res. 2019, 1–8. [Google Scholar] [CrossRef] [PubMed]
  104. Cai, R.; Chen, S.; Long, Y.; Li, C.; Huang, X.; She, Z. Depsidones from Talaromyces stipitatus SK-4, an endophytic fungus of the mangrove plant Acanthus ilicifolius. Phytochem. Lett. 2017, 20, 196–199. [Google Scholar] [CrossRef]
  105. Chang, H.-S.; Cheng, M.-J.; Cheng, M.-J.; Chan, H.-Y.; Hsieh, S.-Y.; Lin, C.-H.; Yech, Y.-J.; Chen, I.-S. Secondary metabolites produced by an endophytic fungus Cordyceps ninchukispora from the seeds of Beilschmiedia erythrophloia Hayata. Phytochem. Lett. 2017, 22, 179–184. [Google Scholar] [CrossRef]
  106. Deng, Z.; Li, C.; Luo, D.; Teng, P.; Guo, Z.; Tu, X.; Zou, K.; Gong, D. A new cinnamic acid derivative from plant-derived endophytic fungus Pyronema sp. Nat. Prod. Res. 2017, 31, 2413–2419. [Google Scholar] [CrossRef] [PubMed]
  107. Gubiani, J.R.; Wijeratne, E.M.K.; Shi, T.; Araujo, A.R.; Arnold, A.E.; Chapman, E.; Gunatilaka, A.A.L. An epigenetic modifier induces production of (10′S)-verruculide B, an inhibitor of protein tyrosine phosphatases by Phoma sp. nov. LG0217, a fungal endophyte of Parkinsonia microphylla. Bioorganic Med. Chem. 2017, 25, 1860–1866. [Google Scholar] [CrossRef] [Green Version]
  108. Kongprapan, T.; Xu, X.; Rukachaisirikul, V.; Phongpaichit, S.; Sakayaroj, J.; Chen, J.; Shen, X. Cytosporone derivatives from the endophytic fungus Phomopsis sp. PSU-H188. Phytochem. Lett. 2017, 22, 219–223. [Google Scholar] [CrossRef]
  109. Kyekyeku, J.O.; Kusari, S.; Adosraku, R.K.; Bullach, A.; Golz, C.; Strohmann, C.; Spiteller, M. Antibacterial secondary metabolites from an endophytic fungus, Fusarium solani JK10. Fitoterapia 2017, 119, 108–114. [Google Scholar] [CrossRef]
  110. Li, X.-B.; Chen, G.-Y.; Liu, R.-J.; Zheng, C.; Song, X.-M.; Han, C.-R. A new biphenyl derivative from the mangrove endophytic fungus Phomopsis longicolla HL-2232. Nat. Prod. Res. 2017, 31, 2264–2267. [Google Scholar] [CrossRef]
  111. Luo, Y.; Chen, W.; Wen, L.; Zhou, L.; Kang, X.; Chen, G. A New Hexanedioic Acid Analogue from the Endophytic Fungus Penicillium sp. OC-4 of Orchidantha chinensis. Chem. Nat. Compd. 2017, 53, 834–838. [Google Scholar] [CrossRef]
  112. Mondol, M.A.M.; Farthouse, J.; Islam, M.T.; Schüffler, A.; Laatsch, H. Metabolites from the Endophytic FungusCurvulariasp. M12 Act as Motility Inhibitors againstPhytophthora capsiciZoospores. J. Nat. Prod. 2017, 80, 347–355. [Google Scholar] [CrossRef]
  113. Siridechakorn, I.; Yue, Z.; Mittraphab, Y.; Lei, X.; Pudhom, K. Identification of spirobisnaphthalene derivatives with anti-tumor activities from the endophytic fungus Rhytidhysteron rufulum AS21B. Bioorg. Med. Chem. 2017, 25, 2878–2882. [Google Scholar] [CrossRef]
  114. Zhu, X.; Zhou, D.; Liang, F.; Wu, Z.; She, Z.; Li, C. Penochalasin K, a new unusual chaetoglobosin from the mangrove endophytic fungus Penicillium chrysogenum V11 and its effective semi-synthesis. Fitoterapia 2017, 123, 23–28. [Google Scholar] [CrossRef]
  115. Maha, A.; Rukachaisirikul, V.; Phongpaichit, S.; Preedanon, S.; Sakayaroj, J. Tyrosine and hydantoin derivatives from the fungus Phoma herbarum PSU-H256 isolated from Hevea brasiliensis. Tetrahedron 2017, 73, 4597–4601. [Google Scholar] [CrossRef]
  116. Elkhayat, E.S.; Goda, A.M. Antifungal and cytotoxic constituents from the endophytic fungus Penicillium sp. Bull. Fac. Pharmacy Cairo Univ. 2017, 55, 85–89. [Google Scholar] [CrossRef]
  117. Sharma, N.; Kushwaha, M.; Arora, D.; Jain, S.; Singamaneni, V.; Sharma, S.; Shankar, R.; Bhushan, S.; Gupta, P.; Jaglan, S. New cytochalasin from Rosellinia sanctae-cruciana, an endophytic fungus of Albizia lebbeck. J. Appl. Microbiol. 2018, 125, 111–120. [Google Scholar] [CrossRef]
  118. Zhang, P.; Li, X.; Yuan, X.-L.; Du, Y.; Wang, B.-G.; Zhang, Y.-M.D.A.Z.-F. Antifungal Prenylated Diphenyl Ethers from Arthrinium arundinis, an Endophytic Fungus Isolated from the Leaves of Tobacco (Nicotiana tabacum L.). Molecules 2018, 23, 3179. [Google Scholar] [CrossRef] [Green Version]
  119. Akhter, N.; Pan, C.; Liu, Y.; Shi, Y.; Wu, B. Isolation and structure determination of a new indene derivative from endophytic fungus Aspergillus flavipes Y-62. Nat. Prod. Res. 2018, 33, 2939–2944. [Google Scholar] [CrossRef]
  120. De Oliveira, D.M.; Pereira, C.B.; Mendes, G.; Junker, J.; Kolloff, M.; Rosa, L.H.; Rosa, C.A.; Alves, T.M.; Zani, C.L.; Johann, S.; et al. Two new usnic acid derivatives from the endophytic fungus Mycosphaerella sp. Zeitschrift für Naturforschung C 2018, 73, 449–455. [Google Scholar] [CrossRef]
  121. Mafezoli, J.; Xu, Y.-M.; Hilário, F.; Freidhof, B.; Espinosa-Artiles, P.; Dos Santos, L.C.; De Oliveira, M.C.; Gunatilaka, A.A.L. Modulation of polyketide biosynthetic pathway of the endophytic fungus, Anteaglonium sp. FL0768, by copper (II) and anacardic acid. Phytochem. Lett. 2018, 28, 157–163. [Google Scholar] [CrossRef]
  122. Xie, J.; Wu, Y.-Y.; Zhang, T.-Y.; Zhang, M.-Y.; Peng, F.-; Lin, B.; Zhang, Y.-X. New antimicrobial compounds produced by endophytic Penicillium janthinellum isolated from Panax notoginseng as potential inhibitors of FtsZ. Fitoterapia 2018, 131, 35–43. [Google Scholar] [CrossRef]
  123. Savi, D.C.; Shaaban, K.A.; Gos, F.M.W.R.; Ponomareva, L.V.; Thorson, J.S.; Glienke, C.; Rohr, J. Phaeophleospora vochysiae Savi & Glienke sp. nov. Isolated from Vochysia divergens Found in the Pantanal, Brazil, Produces Bioactive Secondary Metabolites. Sci. Rep. 2018, 8, 1–10. [Google Scholar] [CrossRef]
  124. Wu, Y.-Z.; Zhang, H.-W.; Sun, Z.-H.; Dai, J.-G.; Hu, Y.-C.; Li, R.; Lin, P.-C.; Xia, G.; Wang, L.; Qiu, B.-L.; et al. Bysspectin A, an unusual octaketide dimer and the precursor derivatives from the endophytic fungus Byssochlamys spectabilis IMM0002 and their biological activities. Eur. J. Med. Chem. 2018, 145, 717–725. [Google Scholar] [CrossRef]
  125. Ibrahim, S.R.M.; Mohamed, G.A.A.; Al Haidari, R.A.; Zayed, M.F.; El-Kholy, A.A.; Elkhayat, E.S.; Ross, S.A. Fusarithioamide B, a new benzamide derivative from the endophytic fungus Fusarium chlamydosporium with potent cytotoxic and antimicrobial activities. Bioorganic Med. Chem. 2018, 26, 786–790. [Google Scholar] [CrossRef]
  126. Maciel, O.M.C.; Tavares, R.S.N.; Caluz, D.R.E.; Gaspar, L.R.; Debonsi, H.M. Photoprotective potential of metabolites isolated from algae-associated fungi Annulohypoxylon stygium. J. Photochem. Photobiol. B Biol. 2018, 178, 316–322. [Google Scholar] [CrossRef]
  127. Wu, X.; Wang, S.; Liu, C.; Zhang, C.; Guo, J.; Shang, X. A new 2H-benzindazole compound from Alternaria alternata Shm-1, an endophytic fungus isolated from the fresh wild fruit of Phellinus igniarius. J. Nat. Med. 2019, 73, 620–626. [Google Scholar] [CrossRef]
  128. Bai, M.; Zheng, C.-J.; Tang, D.-Q.; Zhang, F.; Wang, H.-Y.; Chen, G.-Y. Two new secondary metabolites from a mangrove-derived fungus Cladosporium sp. JS1-2. J. Antibiot. 2019, 72, 779–782. [Google Scholar] [CrossRef]
  129. Noriler, S.A.; Savi, D.C.; Ponomareva, L.V.; Rodrigues, R.; Rohr, J.; Thorson, J.S.; Glienke, C.; Shaaban, K.A. Vochysiamides A and B: Two new bioactive carboxamides produced by the new species Diaporthe vochysiae. Fitoterapia 2019, 138, 104273. [Google Scholar] [CrossRef]
  130. Wang, W.-X.; Li, Z.-H.; He, J.; Feng, T.; Li, J.; Liu, J.-K. Cytotoxic cytochalasans from fungus Xylaria longipes. Fitoterapia 2019, 137, 104278. [Google Scholar] [CrossRef]
  131. Wickramarachchi, S.R.; Samanthi, U.; Wijeratne, K.; Paranagama, P.A. A new antioxidant active compound from the endolichenic fungus, Penicillium citrinum inhabiting the lichen, Parmotrema sp. Int. J. Pharm. Sci. Res. 2019, 10, 3412–3420. [Google Scholar] [CrossRef]
  132. Inose, K.; Tanaka, K.; Koshino, H.; Hashimoto, M. Cyclopericodiol and new chlorinated melleins isolated from Periconia macrospinosa KT3863. Tetrahedron 2019, 75, 130470. [Google Scholar] [CrossRef]
  133. Kumar, S.; Pagar, A.D.; Ahmad, F.; Dwibedi, V.; Wani, A.; Bharatam, P.V.; Chhibber, M.; Saxena, S.; Singh, I.P. Xanthine oxidase inhibitors from an endophytic fungus Lasiodiplodia pseudotheobromae. Bioorganic Chem. 2019, 87, 851–856. [Google Scholar] [CrossRef]
  134. Elissawy, A.M.; Ebada, S.S.; Ashour, M.L.; El-Neketi, M.; Ebrahim, W.; Singab, A.B. New secondary metabolites from the mangrove-derived fungus Aspergillus sp. AV-2. Phytochem. Lett. 2019, 29, 1–5. [Google Scholar] [CrossRef]
  135. Yu, G.; Sun, Z.; Peng, J.; Zhu, M.; Che, Q.; Zhang, G.; Zhu, T.; Gu, Q.; Li, D. Secondary Metabolites Produced by Combined Culture of Penicillium crustosum and a Xylaria sp. J. Nat. Prod. 2019, 82, 2013–2017. [Google Scholar] [CrossRef]
  136. Li, H.-L.; Li, X.-M.; Yang, S.-Q.; Cao, J.; Li, Y.-H.; Wang, B.-G. Induced terreins production from marine red algal-derived endophytic fungus Aspergillus terreus EN-539 co-cultured with symbiotic fungus Paecilomyces lilacinus EN-531. J. Antibiot. 2020, 73, 108–111. [Google Scholar] [CrossRef]
  137. Riga, R.; Happyana, N.; Quentmeier, A.; Zammarelli, C.; Kayser, O.; Hakim, E.H. Secondary metabolites from Diaporthe lithocarpus isolated from Artocarpus heterophyllus. Nat. Prod. Res. 2019, 1–5. [Google Scholar] [CrossRef]
  138. Ma, H.; Wang, F.; Jin, X.; Jiang, J.; Hu, S.; Cheng, L.; Zhang, G. A new diketopiperazine from an endophytic fungus Aspergillus aculeatus F027. Nat. Prod. Res. 2019, 1–6. [Google Scholar] [CrossRef]
  139. Ariefta, N.R.; Nikmawahda, H.T.; Aboshi, T.; Murayama, T.; Tawaraya, K.; Koseki, T.; Katagi, G.; Kakihara, Y.; Shiono, Y. Fusaspirols A-D, novel oxaspirol derivatives isolated from Fusarium solani B-18. Tetrahedron 2019, 75, 1371–1377. [Google Scholar] [CrossRef]
  140. Supratman, U.; Suzuki, T.; Nakamura, T.; Yokoyama, Y.; Harneti, D.; Maharani, R.; Salam, S.; Abdullah, F.F.; Koseki, T.; Shiono, Y. New metabolites produced by endophyte Clonostachys rosea B5-2. Nat. Prod. Res. 2019, 1–7. [Google Scholar] [CrossRef]
  141. Choi, H.G.; Kim, J.W.; Choi, H.; Kang, K.S.; Shim, S.H. New hydroxydecanoic acid derivatives produced by an endophytic yeast Aureobasidium pullulans AJF1 from flowers of Aconitum carmichaeli. Molecules 2019, 24, 4051. [Google Scholar] [CrossRef] [Green Version]
  142. Lee, C.; Li, W.; Bang, S.; Lee, S.J.; Kang, N.-Y.; Kim, S.; Kim, T.I.; Go, Y.; Shim, S.H. Secondary Metabolites of The Endophytic Fungus Alternaria alternata JS0515 Isolated from Vitex rotundifolia and Their Effects on Pyruvate Dehydrogenase activity. Molecules 2019, 24, 4450. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Figure 1. Percentage of metabolites synthesized by endophytes.
Figure 1. Percentage of metabolites synthesized by endophytes.
Ijms 22 00959 g001
Figure 2. Chemical structures of sesquiterpenoids and derivatives.
Figure 2. Chemical structures of sesquiterpenoids and derivatives.
Ijms 22 00959 g002aIjms 22 00959 g002bIjms 22 00959 g002c
Figure 3. Chemical structures of diterpenoids and derivatives.
Figure 3. Chemical structures of diterpenoids and derivatives.
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Figure 4. Chemical structures of other terpenoids and derivatives.
Figure 4. Chemical structures of other terpenoids and derivatives.
Ijms 22 00959 g004aIjms 22 00959 g004b
Figure 5. Chemical structures of polyketides.
Figure 5. Chemical structures of polyketides.
Ijms 22 00959 g005aIjms 22 00959 g005b
Figure 6. Chemical structures of other ketones.
Figure 6. Chemical structures of other ketones.
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Figure 7. Chemical structures of alkaloids and their derivatives.
Figure 7. Chemical structures of alkaloids and their derivatives.
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Figure 8. Chemical structures of penylpropanoids and their derivatives.
Figure 8. Chemical structures of penylpropanoids and their derivatives.
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Figure 9. Chemical structures of lactones.
Figure 9. Chemical structures of lactones.
Ijms 22 00959 g009aIjms 22 00959 g009b
Figure 10. Chemical structures of anthraquinones.
Figure 10. Chemical structures of anthraquinones.
Ijms 22 00959 g010aIjms 22 00959 g010b
Figure 11. Chemical structures of sterides.
Figure 11. Chemical structures of sterides.
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Figure 12. Chemical structures of other new compounds.
Figure 12. Chemical structures of other new compounds.
Ijms 22 00959 g012aIjms 22 00959 g012bIjms 22 00959 g012cIjms 22 00959 g012dIjms 22 00959 g012e
Figure 13. Chemical structures of known compounds.
Figure 13. Chemical structures of known compounds.
Ijms 22 00959 g013
Table 1. Brief summary of new compounds.
Table 1. Brief summary of new compounds.
CompoundMolecular FormulaDegree of UnsaturationColor and MorphologyEndophytic FungusHost PlantSite and NationBiological ActivityRef.
Terpenoids
Sesquiterpenoids and derivatives
1C19H26O7 7brown oilPestalotiopsissp.Tlichen Cetraria islandica (L.) Ach.Yunnan Province,
China
Inhibit the growth of plant pathogenic fungus (1,5)[9]
2C21H28O88
3C21H30O87
4C21H28O88
5C19H26O77
6C15H20O46white powderCo-culture
Strain 307: Trichoderma sp.
the stem bark of Clerodendrum inerme
Bacterium B2: Acinetobacter johnsonii
From an aquaculture pond
Guangdong Province, ChinaShow moderate inhibitory activity against α-glucosidase (7)[10]
7C15H20O46
8C15H24O24colorless gumTrichoderma atroviridebulb of Lycoris radiata.Hubei Province
China
Inactive[11]
9C15H26O3 3white
amorphous powder
Co-culture
Pestalotiopsis sp. fruits of Drepanocarpus lunatus (Fabaceae)
Bacillus subtilis
Weak antibacterial activities (9)[12]
10C15H24O34colorless oi
11C22H32O5 7colorless crystalNectria pseudotrichia 120-1NPInner tissue of Gliricidia sepium healthy stem Cytotoxicity (11–13)[13]
12C26H38O78yellow oil
13C15H26O 3yellow oil
14C15H26O33 Co-culture
Nigrospora oryzae
Irpex lacteus
seeds of Dendrobium officinaleYunnan Province,
China
Anti-AChE activity [14]
15C15H26O2 3white powderEmericella sp. XL 029leaves of Panax notoginsengHebei province,
China
Antifungal activity
Antibacterial activity
(15,16)
[15]
16C15H26O3 3colorless oil
17C19H24O48colorless oilTrichothecium crotocinigenum Antiphytopathogenic activity
(17–20)
[16]
18C19H25ClO57colorless crystals
19C22H28O5 9colorless crystals
20
21C15H22O4 5colorless oilTrichoderma atroviride S361Bark of Cephalotaxus fortuneiZhejiang province, ChinaInactive[17]
22C15H20O4 6white amorphous powderAspergillus sp. xy02leaves of mangrove Xylocarpus moluccensisTrang Province, ThailandAntibacterial activity
(23–24,26,28)
[18]
23
24
25
26colorless oil
27
28
29C15H24O34colorless oilPestalotiopsis adustastem bark of medicinal plant Sinopodophyllum hexandrum (Royle) YingQinling Mountains
China
Weak to moderate cytotoxic activity[19]
30C15H26O23colorless oilF. proliferatum AF-04green Chinese onionLanzhou, China [20]
31C14H24O3 3colorless crystalsTrichoderma asperellum A-YMD-9–2marine
Red alga Gracilaria verrucosa
Yangma Island, Yantai,
China
Potent inhibition of several marine phytoplankton species
31–37
[21]
32C14H20O2 5colorless oil
33
34
35C22H37NO75colorless oil
36
37
38C15H24O44crystal powderAlternaria oxytropisdesert plant
locoweed Oxytropis glabra
Inner Mongolia, ChinaDisplayed an effect on the root growth in Arabidopsis thaliana
(38)
[22]
39colourless oil
40C15H22O45colourless oil
41C15H24O54crystal powder
42C15H22O35colourless oil
43C15H24O54
44C15H26O43
45
46C15H26O33
47
48C15H22O3 5colorless crystalPleosporales sp. SK7mangrove plant Kandelia candel Guangxi Province, China [23]
49C15H22O45yellowish needle crystalsIrpex lacteus DR10-1 waterlogging tolerant plant D. chinenseChongqing
China
Antioxidant activity
Antibacterial activity
[24]
50C15H16O3 8colorless crystalsTrichoderma virens QA-8fresh inner tissue of the medicinal plant Artemisia argyiHubei Province, ChinaAntibacterial
(50–52,55)
Antifungal activity
(50–55)
[25]
51C15H16O48colorless oil
52C15H22O25amorphous powder
53C15H22O35amorphous powder
54C15H24O34colorless oil
55C14H16O47amorphous powder
56C15H26O23colorless needle Alternaria alternateleaves of Psidium littorale Raddi Fujian Province, China [26]
57C15H22O35colorless oilEpicoccum sp. YUD17002
&
Armillaria sp.
rhizomes of the underground portion of Gastrodia elataYunnan Province,
China
[27]
58C15H24O44
59C15H22O25
60C15H22O35
61C15H24O44white amorphous powder
62C29H42O99sticky and optically active oiColletotrichum gloeosporioidesCameroonian medicinal plant Trichilia monadelpha (Meliaceae)Yaounde, Central region, Cameroon [28]
63C17H22O77white powder Penicillium purpurogenum IMM003leaf tissue of the medicinal plant Edgeworthia chrysantha.ChinaShow significant inhibitory activity against pancreatic lipase[29]
64C17H20O78colorless crystals
65C16H20O6 7
66C16H24O3 4yellow oilFusarium oxysporum ZZP-R1coastal plant Rumex madaio MakinoPutuo Island (Zhoushan, China)Moderate antibacterial effect[30]
Terpenoids
Diterpenoids
67C20H30O6 6colorless oilNectria pseudotrichia 120-1NPhealthy stem of Gliricidia sepium Yogyakarta, Indonesia [31]
68C28H39NO3 10amorphous powderDrechmeria sp.root of Panax notoginsengYunnan,
China
Display inhibitory effect (69)
Weak antimicrobial effects.
(68,70,74)
[32]
69C28H37NO511
70C33H45NO512
71C32H43NO712
72C32H43NO712
73C33H45NO712
74C27H33NO512
75C32H33NO917amorphous powderDrechmeria sp. root of Panax notoginsengYunnan province,
China
Display the significant agonistic effect on pregnane X receptor (PXR) (76)[33]
76C32H41NO613
77C26H40O57colorless oilNeosartorya fifischeri JS0553Plant G. littoralisSuncheon, Korea [34]
78C28H39NO310Pale yellow oilAspergillus versicolorfruits of the mangrove Avicennia marinaRed Sea,
Egypt
Weak cytotoxic activity
(79)
[35]
79
80C20H26O48colorless crystalsXylaralyce sp.healthy leaves of Distylium chinenseChinaDisplay brine shrimp inhibiting activity[36]
81C20H26O5 8colorless crystalsApiospora montagneilichen Cladonia sp. [37]
Terpenoids
Other terpenoids
82C26H37NO39colorless oilAspergillus sp. ZJ-68fresh leaves of the mangrove plant Kandelia candelGuangdong Province,
China.
Exhibit inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells (89–91)
Show comparable inhibition of Mycobacterium tuberculosis protein tyrosine phosphatase B
(89)
[38]
83C25H35NO39
84C25H35NO29
85C26H39NO38
86C25H34O39
87C25H36O48
88C25H36O48
89C25H36O48
90C25H34O39
91C25H38O57
92C25H38O37
93C30H40O611yellowish needle crystalsKadsura angustifolia & Penicillium sp. SWUKD4.1850fresh healthy branches of K. angustifoliaChinaModerate cytotoxic activity
(93–100)
[39]
94C30H40O611white needle crystals
95C30H40O6 11white amorphous solid
96C30H40O611
97C32H44O7 11white amorphous powder
98C30H42O610white powder
99C34H46O812yellow amorphous solid
100C31H44O6 10yellow amorphous solid
101C30H46O6 8white amorphous powder
102C17H26O5 5colorless oilPhyllosticta capitalensisleaves of Cephalotaxus fortunei HookShanxi Province,
China
[40]
103C17H24O56
104C17H22O57
105C22H32O67
106C17H26O55
107C15H20O56 Aspergillus versicolor Show weak cytotoxic activities against Hela cells.
(113–114)
[35]
108C15H20O56
109C15H20O56rose-colored oil
110C17H22O67
111C15H20O56
112C15H20O46colorless oil
113C17H22O57
114C17H22O57
115C16H24O55
116C21H32O36yellow oilFusarium oxysporum ZZP-R1coastal plant Rumex madaio MakinoPutuo Island (Zhoushan, China)Antimicrobial activity[30]
117C12H20O43yellow oilDiaporthe lithocarpus A740from the twigs of medicinal plant Morinda officinalisGuangdong province
China
[41]
Ketones
118C20H32O4N26white powderEupenicillium sp. LG41Chinese medicinal plant Xanthium sibiricumChinaCytotoxic activity
Antimicrobial activity (Antibacterial)
[42]
119C38H59O6N10
120C12H18O54colorless crystalsPhomopsis sp. sh917fresh stems of I. eriocalyx var. laxiflflora Kunming, China [43]
121C12H18O54colorless powders
122C11H12O56Brown needles
123C20H26O108colorless needles
124C13H14O57brown solids
125C17H20O3 8white amorphous powder Pestalotiopsis vaccinii (cgmcc3.9199)branch of mangrove plant Kandelia candel (L.) Druce (Rhizophoraceae)coastal and estuarine areas of southern ChinaAnti-enterovirus 7l (EV71)
[44]
126C14H18O46colorless oil
127C12H16O45
128C12H18O44
129C12H14O46
130C17H22O47
131C17H24O56
132C18H28O65
133C17H22O57
134C17H22O57
135C11H12O56pale yellow powderPenicillium chrysogenum MT-12Huperzia serrata (Thunb. ex Murray) Trev.Fujian Province, ChinaExhibit inhibition of nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells
(138,139,142,143,145,146)
[45]
136C9H8O56
137C10H10O56yellow powder
138C15H20O66
139C14H16O67
140C15H16O68pale yellow powder
141C15H18O67
142C15H20O66
143C16H22O76yellow powder
144C15H20O56
145C15H20O56
146C15H20O56
147C14H12O69yellow powderCylindrocarpon sp.fresh roots of Sapium ellipticum Haut Plateaux region, Cameroon [46]
148C14H12O79
149C13H10O79
150C14H12O69yellow crystalsPhomopsis sp. xy21leaves of the Thai mangrove Xylocarpus granatumTrang Province, ThailandWeak anti-HIV activity
(150)
[47]
151C15H16O78colorless crystals
152C15H16O78White amorphous solid
153C15H16O58
154C15H12O610
155C15H10O711
156C17H28O34white powderAspergillus flocculusstem of the medicinal plant Markhamia platycalyx [48]
157C10H10O46colorless crystals Colletotrichum gloeosporioidesmangrove Ceriops tagalHainan Province
China
Show potent antibacterial activity
(157,159)
[49]
158C10H14O44brown oil
159C10H12O35white powder
160C14H18O46amorphous powderParaconiothyrium sp. SW-B-1the seaweed, Chondrus ocellatus HolmesYamagata Prefecture,
Japan
Show moderate antibacterial activity
(164)
[50]
161C14H18O56
162C14H16O67
163C12H16O65
164C22H20O413
165C14H16O67pale brown, amorphous powderAlternaria alternata MT-47medicinal plant of Huperzia serrataFujian Province, ChinaExhibit inhibitory activity on the ATP release of thrombin-activated platelets
(168)
[51]
166C15H12O810pale yellow amorphous powder
167C18H18O910white amorphous powder
168C18H20O99
169C10H11NO46white gumChaetosphaeronema achilleaeshootsEnglish Yew (Taxus baccata), IranWeak antifungal activity and antibacterial activity (170)
Cytotoxicity (169,170)
Biofilm formation (169)
[52]
170C10H10O56
171C27H38O69colorless oil Aspergillus porosusalgal [53]
172C27H38O69
173C26H36O6 9
174C26H36O6 9
175C25H38O37colorless oil Alternaria alternateleaves of Psidium littorale RaddiFujian Province, China [26]
176C29H30O1015amorphous powderPhoma sp. SYSU-SK-7healthy branch of the marine Kandelia candelGuangxi Province,
China
Show strong antibacterial activity
(176)
Exhibit significant antifungal and antibacterial activity (177)
Show significant α-glucosidase inhibitory activity (176–178)
Cytotoxicity (176)
Exhibit radical scavenging activity against DPPH (179)
[54]
177C11H14O45white solid
178C21H24O710
179C13H12O58
180C11H16O34colourless oil
181C10H14O34 Phomopsis sp. D15a2aleaves of Alternanthera bettzickiana (Amaranthaceae)Anambra state of Nigeria [55]
182C11H16O44
183C11H16O44
184C23H26O711Penicillium purpurogenum IMM003fresh healthy leaves of Edgeworthia chrysantha
Zhejiang Province, China [56]
185C22H26O610
186C10H8O57
187C18H27NO46colorless gumCamporesia sambuci FT1061 & Epicoccum sorghinum FT1062healthy fruit of the plant Rhodomyrtus tomentosathe Big Island in Hawaii [57]
188C14H20O65light yellow solidRhytismataceae sp. DAOMC 251461healthy P. mariana needlesNew Brunswick, Canada.Exhibit moderate antifungal activity (189)[58]
189C15H22O65
190C9H12O64colorless platePhomopsis asparagi SWUKJ5.2020fresh, healthy branches of
medicinal plant Kadsura angustifolia
Yunnan province
China
Exhibit notable cytotoxicity
(192–194)
[59]
191C9H12O54
192C9H10O65colorless crystals
193C11H14O45colorless plates
194C11H14O55
195C14H18O4 6colorless oilDendrothyrium variisporumroots of the Algerian plant Globularia alypumAin Touta, Batna 05000 (Algeria) [60]
196C18H24O57
197C11H10O5 7colorless oilAlternaria sp.twigs of Morinda offificinalisGuangdong province
China
[61]
198C12H11O5 8yellow oil
199C8H12O33colorless gumTrichoderma atroviridebulb of Lycoris radiataHubei Province
China
[11]
200C13H14O5 7yellow viscous liquidEurotium chevalieri KUFA 0006healthy twig of Rhizophora mucronata PoirChanthaburi Province, Eastern ThailandPrevent biofilm formation[62]
201C9H14O4 3colorless gumSimplicillium sp. PSU-H41leaf of Hevea brasiliensisSongkhla Province Thailand [63]
202C15H12O8 10yellowish crystalCytospora rhizophoraeMorinda offificinalisGuangdong province
China
Exhibit weak growth inhibitory activity against the tumor cell lines
(202)
[64]
203C14H10O610brown gum
204C14H8O711yellowish green powder
205C13H16O5 6yellow gumFusarium sp. HP-2Chinese agarwood “Qi-Nan”Hainan Province
China
Show weak acetylcholinesterase inhibitory activity (207)[65]
206C14H14O48red crystals
207C16H18O6 8red solid
208C18H17ClO710yellowish powderPenicillium citrinum HL-5126 mangrove Bruguiera sexangula var. rhynchopetala South China SeaDisplay cytotoxic activity (209)
Show weak antibacterial activity
(208)
[66]
209C18H18O7 10
210C13H16O56amorphous white powder Phoma sp. PF2Artemisia princeps Show moderate inhibitory activities on nitric oxide levels
(210–211)
[67]
211C14H18O56
212C25H26O513polar yellow solidAspergillus sp. ASCLAhealthy leaf tissue of the medicinal plant Callistemon subulatus Exert moderate-high activities against Staphylococcus aureus[68]
213C12H18O34white powderCylindrocarpon sp.fresh roots of Sapium ellipticumHaut Plateaux region, Cameroon [46]
214C25H28O612yellow oilDiaporthe lithocarpus A740twigs of medicinal plant Morinda officinalis. Guangdong province
China
[41]
Alkaloids and their derivatives
215C26H33O8N 11 Apiospora montagneilichen Cladonia sp. [37]
216C16H19NO38colorless amorphous solid Chaetomium globosum CDW7 [69]
217C17H24N2O3 7colorless crystalsPenicillium citrinum HL-5126 mangrove Bruguiera sexangula var. rhynchopetalaSouth China Sea [66]
218C13H15NO27colorless powderBionectria sp.seeds of the tropical plant Raphia taedigeraHaut Plateaux region, Cameroon [70]
219C16H15NO510yellow powderCylindrocarpon sp.fresh roots of Sapium ellipticumHaut Plateaux region, Cameroon [46]
220C14H21NO5 5white powder
221C26H29NO6 13pale yellow amorphous solidAspergillus versicolorleaves of the Egyptian water hyacinth Eichhornia crassipes EgyptExhibit moderate antiproliferative activity[71]
222C17H15NO8 11white amorphous solidPestalotiopsis flavidulabranches of Cinnamomum camphoraYunnan province
china
Moderate cytotoxicity
(222–223)
[72]
223
224C19H24N2O2 9white amorphous powderIrpex lacteus-Amedicinal plant Huperzia serrataFujian Province
China
Show moderate neuroprotective activity
(224–225)
[73]
225C19H24N2O29
226C14H17NO37colorless solidAlternaria alternateleaves of Psidium littorale Raddi Fujian Province, China [26]
227C27H31N3O5 14brilliant yellowish oilFusarium sambucinum TE-6Lfresh leaves of cultivated tobacco (N. tabacum L.). N. tabacum L. Hubei province
China
Show potent inhibitory effects
(227–228)
Exhibit remarkable larvicidal activity (228)
[74]
228C27H31N3O514white solid
Penylpropanoids and their derivatives
229C10H14O54clear solidMycosphaerellaceae sp. DAOMC
250863
healthy needles from Picea rubens (red spruce) and P. mariana (black spruce)Eastern CanadaShow modest antibiotic activity to E. coli[58]
230C16H18O48light-yellow powderC. globosum CDW7Ginkgo bilobaChinaShow moderate antifungal activity[69]
231C12H14O46colorless amorphous solidPestalotiopsis sp. HHL-101fresh twigs of the mangrove plant Rhizophora stylosaHainan Island, ChinaExhibit moderate antibacterial activity [75]
232C12H12O4 7white amorphous powderNectria pseudotrichia 120–1NPhealthy stem of Gliricidia sepiumYogyakarta, Indonesia [31]
233C13H14O4 7
234C21H12O12 16off-white amorphous solidAspergillus versicolorleaves of the Egyptian water hyacinth Eichhornia crassipes Egypt [71]
235C22H14O1216yellowish amorphous powder
236C21H22O611colorless crystalsPestalotiopsis adustastem bark of wild rare medicinal plant Sinopodophyllum hexandrum (Royle) YingQinling Mountains
China
Show weak to moderate cytotoxic activity[19]
237C13H14O77white solid powder T. harzianum Fes1712Rubber Tree Ficus elastica LeavesChinaExhibit inhibitory activity against Gram-negative bacteria
(237–238)
[76]
238
239C11H12O6 6white amorphous powder Penicillium coffeae MA-314fresh inner tissue of the leaf of marine mangrove plant Laguncularia racemosaHainan island, China [77]
240
241C18H22O3 8yellow oilDiaporthe sp.branches of Pteroceltis tatarinowii MaximNanjing province, ChinaShow modest antibacterial activity
Weak cytotoxicity
[78]
Lactones
242C11H10O5 7yellowish brown solidAlternaria sp. seeds of the plant Ziziphus jujubaUzbekistan [79]
243C16H26O64white, amorphous powderPhaeoacremonium sp.leaves of Senna spectabilisAraraquara Cerrado area, Sao Paulo state, Brazil.Exhibit antifungal activity
(244–245)
Cytotoxicity (244)
[80]
244C16H26O54
245
246C9H12O24amorphous powderXylaria curta 92092022barksTaiwan
China
Show moderate antibacterial and phytotoxic activities[81]
247C16H22O56white powderTrichoderma sp. 307 & Acinetobacter johnsonii B2Strain 307, stem bark of Clerodendrum inermeGuangdong Province, ChinaExhibit potent α-glucosidase inhibitory activity (247–248)
show moderate inhibitory activity against α-glucosidase (249)
[10]
248C16H20O57
249colorless needles
250C10H16O3 3colorless oilPestalotiopsis sp.fruits of Drepanocarpus lunatus (Fabaceae) [12]
251C13H18O55
252C11H14O55colorless crystalsTalaromyces sp.Xanthoparmelia angustiphyllaStockholm, SwedenExhibit selective cytotoxicities[82]
253C32H50O78yellow powderMutant CS/asm21-4Maytenus hookeriChinaExhibit antibacterial activity[83]
254C22H21NO4 13light yellow gumAspergillus terreusYongxing Island fresh, healthy leaves of S. maritima L.South China Sea, ChinaShow strong inhibitory effects on the production of NO (256–257) [84]
255C22H19O414
256C22H21NO513
257C22H21NO513
258C20H22O310yellow oilAspergillus sp.root of Tripterygium wilfordiiWuhan, ChinaExhibited weak AchE and BACE1 inhibitory activity (260–261)
Showed excellent inhibitory effects on the production of IL-1β, TNF-α, and NO
(258–261)
[85]
259C24H26O612yellow oil
260C24H26O612colorless oil
261C23H26O611
262C22H36O85oilH. fuscumlichen Usnea sp.Yunnan, ChinaExhibit moderate cytotoxicity[86]
263C26H34O1210white powderTalaromyces purpurogenusfresh leaves of the toxic medicinal plant Tylophora ovataChina [87]
264C28H36O1211
265C26H40O97
266C11H18O3 3yellow oilPenicillium coffeae MA-314 fresh inner tissue of the leaf of marine mangrove plant Laguncularia racemosaHainan island, ChinaExhibit potent antifungal activity[77]
267C12H12O57brown solidsPhomopsis sp.stems of Isodon eriocalyx var. laxiflfloraKunming, China [43]
268C17H14O311white amorphous powderPhyllosticta sp. J13-2-12Yleaves of Acorus tatarinowii Guangxi Province, China [88]
269
270C19H16O512colorless oil
271C16H12O311colorless crystal
272C22H26O6 10luminous yellow oilPestalotiopsis microsporafruits of Manilkara zapotaKandy, Sri Lanka [89]
Anthraquinones
273C12H14O56yellow amorphous powder.Penicillium citrinum Salicorn 46Salicornia herbacea Torr.China [90]
274C14H14O4Cl2 7yellow oil Lachnum cf. pygmaeum DAOMC 250335dead P. rubens twigNB, CanadaInhibit the growth of M. violaceum,[58]
275C16H12O611 Apiospora montagneilichen Cladonia sp. [37]
276C18H14O712yellow crystalEurotium chevalieri KUFA 0006healthy twig of Rhizophora mucronata Poir.Chanthaburi Province, Eastern ThailandCause a significant reduction in biofilm production[62]
277C15H16O38 Nigrospora oryzae co-cultured with Irpex lacteusseeds of Dendrobium offifficinaleYunnan Province
China
[14]
278C15H18O27
279C15H20O46
280C15H20O66
281C14H16O27Phoma betaeKalidium foliatum (Pall.)ChinaCytotoxic activities
(281)
[91]
282C14H16O37
283C14H20O55
284C27H24O1016red powderNeofusicoccum austral SYSU-SKS024branches of the mangrove plant Kandelia candelGuangxi province,
China
Show inhibitory effects against Indoleamine 2,3-dioxygenase (IDO)[92]
285C15H16O68yellow powder
286C14H18O56white powder
287C16H18O58yellow amorphous powderNectria pseudotrichia 120-1NP healthy stem of Gliricidia sepiumYogyakarta, IndonesiaExhibit antibacterial activity
Exhibit cytotoxicity
[31]
288C30H22O1220yellow powderARL-09 (Diaporthe sp.)Anoectochilus roxburghiiChinaCytotoxicity
Effects on NF-κB signaling pathway
[93]
289C40H45NO10S19red powderCS/asm21-4callus of Chinese medicinal plant Maytenus hookeriChinaShow moderate antimicrobial activities (antibacterial activities and antifungal activity)
(289–291)
[83]
290C40H49NO1217yellow powder
291C40H44NO8Cl 19
292C12H18O64colorless oilXylaria sp. SYPF 8246root of Panax notoginsengYunnan, China [94]
293C15H14O69 Talaromyces funiculosuslichen thallus of Diorygma hieroglyphicumIndiaDisplay antimicrobial activity [95]
294C16H14O7 10yellow gumSimplicillium lanosoniveum Zare & W. Gams PSU-H168 and PSU-H261 leaves of Hevea brasiliensisSongkhla Province, ThailandDisplay antifungal activity[96]
295C17H18O7 9red amorphous powderFusarium napiformemangrove plant, Rhizophora mucronataMakassar, IndonesiaExhibit moderate antibacterial activity (295–296)
Phytotoxic (295–296)
[97]
296C16H16O69orange amorphous powder
Sterides
297C34H52O89faint yellow oilXylaria sp.leaves of Panax notoginsengYunnan province
China
Show cytotoxicity
(297)
[98]
298C28H44O77semitransparent oil
299C25H36O58colorless needleChaetomium sp. M453 Chinese herbal medicine Huperzia serrataYunnan Province, ChinaShow weak acetylcholinesterase inhibitory activity
(302)
[99]
300C25H36O5 8colorless amorphism
301C25H34O5 9
302C28H42O38yellow oil
303C22H32O3 7colorless crystalsStemphylium sp. AZGP4–2root of Polyalthia lauiHainan Province China Show antibacterial activity against Escherichia coli (303)
Exhibit antibacterial activity
(304)
[100]
304C23H36O36
305C23H34O37colorless needle crystals
306C44H72O29white amorphous powderFusarium sp.Mentha longifolia L. (Labiatae) rootsSaudi ArabiaPossessed 5-LOX inhibitory potential
(306–308)
[101]
307C28H46O3 6
308C30H48O5 7
309C28H40O29colorless powderPleosporales sp. F46 and Bacillus wiedmannii. Com1medicinal plant Mahonia fortuneiQingdao, China.Exhibit moderate antibacterial efficacy[102]
310C32H41NO313white powerAspergillustubingensis YP-2bark of Taxus yunnanensis Yunnan Province, ChinaShow weak cytotoxicities
(311)
[103]
311C22H34O36
Other types of compounds
312C21H24O6 10colorless oilTalaromyces stipitatus SK-4leaves of a mangrove plant Acanthus ilicifoliusGuangxi Province, ChinaShow antibacterial activity and inhibitory against α-glucosidase
(313)
[104]
313C23H26O711
314C15H21NO86whitish needlesC. ninchukispora BCRC 31900seeds of medicinal plant Beilschmiedia erythrophloia HayataTaiwan
China
Show anti-inflammatory effects through inhibition of NO production
(317,314–315)
[105]
315C15H21NO76
316C16H23NO76
317C15H21NO86yellowish solid
318C15H16O5 8white amorphous powderPyronema sp. (A2-1 & D1-2)Taxus maireiHubei province, ChinaExhibit moderate antibiotic activity[106]
319C11H16O4 4yellow oilPhoma sp. nov. LG0217branches of Parkinsonia microphyllaTucson, Arizona [107]
320C12H16O4 5colorless amorphous powderPenicillium citrinum Salicorn 46Salicornia herbacea TorrChinaExhibit potent cytotoxic activity[90]
321C21H29NO98colorless gumPhomopsis sp. PSU-H188midrib of Hevea brasiliensisTrang Province, Thailand [108]
322C20H28O77
323C21H27O6N 9yellow amorphous solidFusarium solani JK10root of the Ghanaian medicinal plant Chlorophora regiaEastern Region of GhanaExhibit antibacterial efficacies
(325–326,328)
[109]
324
325C21H27O7N9
326
327C21H25O8N10
328C22H29O7N9pale yellow amorphous solid
329C22H29O5N9yellow amorphous solid
330C14H14O4 8colourless oilPhomopsis longicolla HL-2232fresh healthy leaf of Brguiera sexangula var. rhynchopetala South China Sea Show moderate antibacterial activities[110]
331C9H16O42white needlesPenicillium sp. OC-4leaves of Orchidantha chinensisGuangdong Province, ChinaDisplay strong antioxidant activity[111]
332C16H24O65colorless, amorphous solidCurvularia sp.leaf of the medicinal plant Murraya koenigiiBangladeshExhibit zoospore motility impairment activity
(333–334)
[112]
333C12H18O64
334C10H12O35colorless crystals
335C10H16O43colorless oil
336C20H16O513yellow viscous oilRhytidhysteron rufulum AS21Bleaves of Azima armentosaSamutsakhon province, Thailand Display the most promising anti-tumor activity
(337)
[113]
337C22H18O514pale yellow gum
338C11H12O46brown solidsPhomopsis sp. sh917stems of Isodon eriocalyx var. laxifloraKunming, China [43]
339C15H15NO39brown gumDendrothyrium variisporumroots of the Algerian plant Globularia alypumAlgeriaShow the strongest activity against Bacillus subtilis and Micrococcus luteus (339) [60]
340C14H13NO29
341C12H17NO35
342C15H18N2O48light yellow gumTrichoderma atroviridebulb of Lycoris radiatachina [11]
343C32H34N2O417yellow crystal.Penicillium chrysogenum V11vein of Myoporum bontioides A. GrayLeizhou Peninsula, ChinaDisplay significant antifungal activity and remarkable cytotoxicities [114]
344C14H15NO 8yellow crystalEurotium chevalieri KUFA 0006healthy twig of Rhizophora mucronata Poir.Chanthaburi Province, Eastern ThailandShow inhibition of biofilm production
(344–345)
[62]
345C14H15NO 8yellowish viscous liquid
346C13H15NO37
347C18H18O610colorless solidSimplicillium sp. PSU-H41leaf of Hevea brasiliensis (Euphorbiaceae)Songkhla, ThailandDisplay weak antibacterial against Staphylococcus aureus
(347)
Exhibit weak antifungal activity against Cryptococcus neoformans
(349)
[63]
348C19H20O6 10pale yellow solid
349C20H20O6 11
350C25H24O7 14
351
352C25H22O815yellow gum
353C24H26O712pale yellow gum
354C34H30O11 20colorless solid
355C31H28O8 18pale yellow gum
356C17H24N2O67colorless viscous oilPhoma herbarum PSU-H256leaf of Hevea brasiliensisSongkhla, Thailand [115]
357C12H13NO6 7
358C16H19NO78
359C15H17NO5 8
360C7H12N2O33
361C14H14N2O59
362C11H12O36white amorphous solid.Penicillium sp.leaf of Senecio flavus (Asteraceae)Al-Azhar University EgyptShow antifungal activity and cytotoxic activity[116]
363C30H37NO7 13white amorphous powderR. sanctae-crucianaleaves of the medicinal plant A. lebbeck.IndiaShow considerable cytotoxic potential[117]
364C24H30O410yellowish oilArthrinium arundinis TE-3 fresh leaves of cultivated tobacco Hubei Province ChinaShow selective antifungal activity
(364–365)
Display moderate in vitro cytotoxicity (365)
[118]
365C20H24O49
366C20H24O39
367C23H24O512brown powderAspergillus flavipes Y-62stems of plant Suaeda glauca (Bunge) BungeZhejiang province, East ChinaShow weak antimicrobial activity [119]
368C16H14O69colorless crystalsMycosphaerella sp. (UFMGCB2032)healthy leaves of Eugenia bimarginataAtlanta, GA, USAExhibit moderate antifungal activities[120]
369C17H18O99colorless solid
370C20H16O5 13off-white gumAnteaglonium sp. FL0768Living photosynthetic tissue of sand spikemoss (Selaginella arenicola; Selaginellaceae) [121]
371C28H26N2O5 17amorphous light yellow powderPenicillium janthinellum SYPF 7899three-year-old healthy P. notoginsengYunnan province, ChinaExhibit significant inhibitory activities
(371–373)
[122]
372
373C15H19NO6 7brown oil
374C14H24O4 3colorless oilPhaeophleospora vochysiae sp. novVochysia divergenswetland in BrazilShow considerable antimicrobial activity [123]
375C12H17NO6 5colorless oilBionectria sp.fresh seeds of R. teadigeraHaut Plateaux region, Cameroon [70]
376C18H14N2O613white powder
377C13H19NO45yellowish oilTrichoderma atroviride S361bark of Cephalotaxus fortuneiZhejiang province, China [17]
378
379C18H20O79amorphous powderXylaria sp. SYPF 8246root of Panax notoginsengWenshan, Yunnan, ChinaDisplay significant inhibitory activities against human carboxylesterase 2 (hCE 2)
(379,383–385)
[94]
380C12H10O58colorless oil
381C12H18O64
382C12H20O53
383C19H22O79
384C19H21O7Cl9
385C18H19O7Cl9
386C32H42O412brown oilByssochlamys spectabilisleaf tissue of the medicinal plant Edgeworthia chrysanthaZhejiang Province, Chinaweakly active against Escherichia coli and Staphyloccocus aureus
(388)
Display selective inhibitory effects toward hCE2-mediated FD hydrolysis
(386)
[124]
387C16H22O37yellow oil
388C16H26O25
389C20H29N5O69white amorphous powderFusarium chlamydosporiumAnvillea garcinii (Burm.f.) DC. leaves EgyptExhibit selective antifungal activity and cytotoxic effect
possess high antibacterial potential
[125]
390C15H16N2O29 Annulohypoxylon stygiumred seaweed Bostrychia radicansUbatuba city, São Paulo State, Brazil [126]
391C23H16O2N217purple-red powderAlternaria alternata Shm-1fresh wild body of Phellinus igniariusShanxi Province, China [127]
392C10H12O65colorless crystalsCladosporium
sp. JS1–2
mangrove Ceriops tagalHainan Province in ChinaShow moderate antibacterial activities (392–393)
Showed growth inhibition activities against newly hatched larvae of H. armigera Hubner
(392–393)
[128]
393C10H14N2O25yellow powder
394C8H13NO43white solidDiaporthe vochysiae sp. nov. (LGMF1583)medicinal plant Vochysia divergens Display considerable antibacterial activity
(395)
Show low to moderate cytotoxic activity
(394–395)
[129]
395C11H17NO4 4white solid
396C28H40O69yellow oilDiaporthe lithocarpus A740Twigs of medicinal plant Morinda officinalisGuangdong province
, China
Show weak cytotoxic activity
(396–397)
[41]
397C28H40O69
398C30H37O7N13colorless powderXylaria longipes Ailao Moutain [130]
399C30H39O9N12
400C32H41O8N13
401
402C30H37NO713
403C18H18O710 Penicillium citrinumParmotrema sp. Hakgala montane forest in Sri LankaShow moderate antioxidant activity[131]
404C11H11ClO56 Periconia macrospinosa KT3863a terrestrial herbaceous plantKanagawa prefecture,
Japan
[132]
405C12H13ClO46
406C7H12O32light yellow liquidLasiosdiplodia pseudotheobromae Exhibite XO inhibition (407)
oxidized form of 406 show high XO inhibition
[133]
407C13H22O33
408C17H16O810pale-yellow needlesPleosporales sp. SK7leaves of the mangrove plant Kandelia candelGuangxi Province, China [23]
409C15H19N2O28faint yellow oilAspergillus sp. AV-2 inner healthy leaves of mangrove plant Avicennia marinaHurghada, Egypt [134]
410C19H22O59yellow powder
411C10H14O34yellowish oilIrpex lacteus DR10-1 Roots of waterlogging tolerant plant Distylium chinenseChongqing in the TGR area, ChinaExhibit strong antioxidant activity
(413)
Show moderate antibacterial activity
(411–413)
[24]
412C10H14O34
413C12H16O45brown flaky solid
414C33H50O69pale yellow oilPenicillium crustosum PRB-2 & Xylaria sp. HDN13-249Xylaria sp. HDN13-249:
root of Sonneratia caseolaris
Hainan province, ChinaShow antibacterial activity
(415–416)
Show promising activity against M. phlei
(416)
[135]
415C33H50O9S 9
416C24H40O55pale yellow oilsXylaria sp. HDN13-249
417C24H40O8S 5
418C9H14O23colorless oilAspergillus terreus EN-539 & Paecilomyces lilacinus EN-531inner tissues of the marine red alga Laurencia okamuraiChinaExhibit inhibitory activity against bacteria and fungi[136]
419C23H20O5 14white powderDiaporthe lithocarpusleaves of Artocarpus heterophyllusDortmund, Germany [137]
420C16H20N2O4 8colourless oilAspergillus aculeatus F027fresh leaves of Ophiopogon japonicus (Linn. f.) Ker-GawlHubei province of China [138]
421C17H20O68reddish oilFusarium solani B-18inner tissue of the unidentifified forest littersMount Merapi area Sleman, Yogyakarta, Indonesia.Activat a signaling pathway in osteoclastic differentiation of murine macrophage (421)[139]
422C17H20O68yellow oil
423C15H18O57reddish oil
424C15H18O57pale-yellow oil
425C16H20O57amorphous powderHypoxylon fusculichen Usnea sp.Lilong Snow Mountain in Lijiang, Yunnan, ChinaExhibit moderate cytotoxicity
(426–427)
[86]
426C21H36O64white solid
427C18H30O7 4white powder
428C18H28O65
429C25H24O6 14colorless gumSimplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261leaves of Hevea brasiliensisSongkhla Province, ThailandExhibit antibacterial activity
(430)
Display antifungal activity
(430–431)
[96]
430C32H34O816
431C16H14O7 10yellow gum
432C14H20O45white amorphous powderClonostachys rosea B5-2 mangrove plants Garut, IndonesiaExhibit phytotoxicity against lettuce seedlings (432)[140]
433C7H10O33colourless oil
434C9H12O34white amorphous powder
435C9H14O43
436C26H32O1211white powderTalaromyces purpurogenusfresh leaves of the toxic medicinal plant Tylophora ovataGuangxi Province, ChinaShow significant inhibitory activity against NO production in LPS-induced RAW264.7 cells
(436)
Show moderate inhibitory activities toward XOD and PTP1b
(437,441)
[87]
437C26H38O118white powder
438C27H28O814white powders
439C29H40O910
440C27H40O78
441C26H34O710
442C22H32N4O5 9white powderPhomopsis sp. D15a2a leaves of Alternanthera bettzickiana (Amaranthaceae)Anambra state of Nigeria [55]
443C8H13NO53
444C20H38O72colorless oilAureobasidium pullulans AJF1flower of Aconitum carmichaeli,Jangbaek Mountain, Gangwon-do, Korea [141]
445C30H56O103
446C16H14O810yellow amorphous powderAlternaria alternata JS0515Vitex rotundifolia (beach vitex)Suncheon, Korea [142]
447C23H27O5Cl10colorless oilArmillaria sp. & Epicoccum sp. YUD17002YUD17002: rhizomes of the underground portion of Gastrodia elataYunnan
Province, China
Exhibit moderate in vitro cytotoxic activities (447)
Show weak acetylcholinesterase Inhibitory activity (447)
[27]
448C10H10O46white amorphous powder
449C14H20O95light-yellow oil
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Zheng, R.; Li, S.; Zhang, X.; Zhao, C. Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study. Int. J. Mol. Sci. 2021, 22, 959. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020959

AMA Style

Zheng R, Li S, Zhang X, Zhao C. Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study. International Journal of Molecular Sciences. 2021; 22(2):959. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020959

Chicago/Turabian Style

Zheng, Ruihong, Shoujie Li, Xuan Zhang, and Changqi Zhao. 2021. "Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study" International Journal of Molecular Sciences 22, no. 2: 959. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020959

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