Abstract
Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy.
Keywords: Sesquiterpenes, macrocyclic trichothecenes, cytotoxicity, anti-cancer activity, roridin, mode of action, structure-activity relationships.
Current Medicinal Chemistry
Title:Macrocyclic trichothecenes as antifungal and anticancer compounds
Volume: 23 Issue: 1
Author(s): Maira Peres de Carvalho, Herbert Weich and Wolf-Rainer Abraham
Affiliation:
Keywords: Sesquiterpenes, macrocyclic trichothecenes, cytotoxicity, anti-cancer activity, roridin, mode of action, structure-activity relationships.
Abstract: Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy.
Export Options
About this article
Cite this article as:
de Carvalho Peres Maira, Weich Herbert and Abraham Wolf-Rainer, Macrocyclic trichothecenes as antifungal and anticancer compounds, Current Medicinal Chemistry 2016; 23 (1) . https://dx.doi.org/10.2174/0929867323666151117121521
DOI https://dx.doi.org/10.2174/0929867323666151117121521 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Gene Expression-Based Pharmacodynamic Biomarkers: The Beginning of a New Era in Biomarker-Driven Anti-Tumor Drug Development
Current Molecular Medicine Natural Radioprotective Agents: An Overview
Current Organic Chemistry Preface [Hot Topic: Anti-Cancer Agents (Executive Editors: A.P. Kozikowski and M. Pellecchia)]
Current Pharmaceutical Design Multicomponent Reactions in Antimitotic Drug Discovery
Current Topics in Medicinal Chemistry Assessment of the Impact of Flavoring on the Nutritional Content of Potato Chips
Current Nutrition & Food Science Classification of Human Pregnane X Receptor (hPXR) Activators and Non-Activators by Machine Learning Techniques: A Multifaceted Approach
Combinatorial Chemistry & High Throughput Screening Vitamin D and the Adaptive Immune System with Special Emphasis to Allergic Reactions and Allograft Rejection
Inflammation & Allergy - Drug Targets (Discontinued) Mediterranean Diet And Longevity: An Example Of Nutraceuticals?
Current Vascular Pharmacology Isolation and Boactivities of Furfuran Type Lignan Compounds from Edible Plants
Recent Patents on Food, Nutrition & Agriculture Subject Index To Volume 1
Current Gene Therapy Novel Approaches to Study the Involvement of α7-nAChR in Human Diseases
Current Drug Targets Black Currant Anthocyanins Abrogate Oxidative Stress through Nrf2- Mediated Antioxidant Mechanisms in a Rat Model of Hepatocellular Carcinoma
Current Cancer Drug Targets Microbial / Enzymatic Synthesis of Chiral Intermediates for Pharmaceuticals: Case Studies from BMS
Current Organic Chemistry Optical Sensors for Detection of Amino Acids
Current Medicinal Chemistry Recent Advances in Superparamagnetic Iron Oxide Nanoparticles for Cellular Imaging and Targeted Therapy Research
Current Pharmaceutical Design Preclinical and Clinical Studies of Novel Breast Cancer Drugs Targeting Molecules Involved in Protein Kinase C Signaling, the Putative Metastasis-Suppressor Gene Cap43 and the Y-box Binding Protein-1
Current Medicinal Chemistry Cancer Treatment-Induced Cardiotoxicity: a Cardiac Stem Cell Disease?
Cardiovascular & Hematological Agents in Medicinal Chemistry Proteomic Profiling of a Biomimetic Drug Delivery Platform
Current Drug Targets Cheminfomatic-based Drug Discovery of Human Tyrosine Kinase Inhibitors
Current Topics in Medicinal Chemistry BCL-2 Family Proteins: The Mitochondrial Apoptotic Key Regulators
Current Cancer Therapy Reviews