Synthesis and Toxicity Evaluation of New Pyrroles Obtained by the Reaction of Activated Alkynes with 1-Methyl-3-(cyanomethyl)benzimidazolium Bromide
Abstract
:1. Introduction
2. Results and Discussions
2.1. Chemistry
2.2. Toxicity Evaluation
2.2.1. Plant Toxicity Evaluation
2.2.2. Animal Toxicity Evaluation
Artemia Franciscana Toxicity Assay
Daphnia Magna Toxicity Assay
2.3. Prediction of the Molecular Mechanism of Action and Toxicity
2.3.1. PASS Prediction
2.3.2. Predicted Acute Rat Toxicity
3. Materials and Methods
3.1. Chemistry
3.1.1. Synthesis of 1-Methyl-3-cyanomethyl-benzimidazolium Bromide 13
3.1.2. General Procedure for the Synthesis of Pyrroles 17a–f
3.2. Toxicity Evaluation
3.2.1. Phytotoxicity Evaluation
3.2.2. Animal Toxicity Assay
Artemia Franciscana Toxicity Assay
Daphnia Magna Toxicity Assay
3.3. Prediction of the Molecular Mechanism of Action and Compounds’ Toxicity
3.4. Statistical Analyses
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Chemical Formula | C15H15N3O2 |
---|---|
Mr | 269.30 |
Crystal system | monoclinic |
Space group | P21/c |
Temperature (K) | 180 |
a, b, c (Å) | 11.3092(4), 11.6261(4), 10.8025(4) |
β(°) | 96.930(4) |
V(Å3) | 1409.96(10) |
Z | 4 |
ρcalcd (g cm−3) | 1.269 |
Crystal size (mm) | 0.30 × 0.20 × 0.15 |
μ (MoKα) (mm−1) | 0.087 |
2Θ range | 3.628 to 58.318 |
Reflections collected | 8712 |
Independent reflections | 3261 |
Rint | 0.0280 |
No. of parameters | 183 |
No. of restraints | 0 |
R1obs | 0.0477 |
wR2obs | 0.1008 |
R1all | 0.0703 |
wR2all | 0.1137 |
GOF | 1.037 |
F(000) | 568 |
completeness Θmax | 99.99% |
largest diff. peak/hole (e Å–3) | 0.15/−0.25 |
CCDC No. | 2007999 |
Compound | LC 15024h (µM) | 95% CI 224h (µM) | LC5048h (µM) | 95% CI48h (µM) |
---|---|---|---|---|
13 | 259.9 | 222.4–303.7 | 136.0 | 110.2–167.9 |
17a | 179.6 | 127.6–252.9 | 64.8 | 47.77–87.86 |
17b | 121.3 | 89.7–164.0 | ND * | 13.27–43.19 |
17c | ND * | 3.0–134.2 | ND * | ND * |
17d | 889.6 | 850.7–930.2 | 410.4 | ND ** |
17e | 970.6 | 892.7–1055 | 496.2 | 408.9–602.1 |
17f | 149.6 | 119.0–188.1 | ND * | ND * |
Nifedipine | ND * | ND * | 8.3 | 7.1–9.7 |
Activity | 17a | 17b | 17c | 17d | 17e | 17f | Nifedipine |
---|---|---|---|---|---|---|---|
Anti-ischemic cerebral | 0.43 | 0.53 | 0.59 | 0.67 | 0.38 | 0.46 | 0.65 |
Anti-ischemic | 0.28 | 0.36 | 0.35 | 0.41 | 0.34 | 0.33 | 0.87 |
Antianginal | - | 0.44 | 0.48 | 0.55 | 0.38 | 0.43 | 0.81 |
Calcium channel (voltage-sensitive) activator | 0.36 | 0.45 | 0.43 | - | 0.53 | 0.51 | 0.68 |
Cardiotonic | 0.33 | 0.38 | 0.39 | 0.41 | 0.45 | 0.46 | 0.41 |
Calcium channel blocker | - | 0.29 | 0.34 | 0.32 | 0.28 | 0.32 | 0.72 |
Antihypertensive | - | 0.30 | 0.32 | 0.39 | 0.20 | 0.23 | 0.97 |
Activity | 17a | 17b | 17c | 17d | 17e | 17f |
---|---|---|---|---|---|---|
Anti-arthritic | 0.67 | 0.61 | 0.58 | 0.51 | - | - |
Interleukin antagonist | 0.63 | 0.54 | 0.50 | 0.48 | - | - |
Interleukin 2 antagonist | 0.48 | 0.43 | 0.38 | 0.36 | - | - |
Rheumatoid arthritis treatment | 0.40 | 0.46 | 0.46 | 0.37 | 0.36 | 0.37 |
Compound | Oral LD50 (mg/kg) | Oral LD50 Class | IV LD50 (mg/kg) | IV LD50 Class |
---|---|---|---|---|
17a | 1984 | 4 | 65.75 | 4 |
17b | 1412 * | 4 * | 71.56 | 4 |
17c | 981 | 4 | 67.30 | 4 |
17d | 809.8 * | 4 * | 40.72 | 4 |
17e | 1735 * | 4 * | 120.60 | 4 |
17f | 914.6 | 4 | 85.54 | 4 |
nifedipine | 1225 | 4 | 57.46 | 4 |
18a | 513.6 * | 4 * | 23.99 | 3 |
18b | 1792 | 4 | 69.14 | 4 |
18c | 877.6 * | 4 | 46.77 | 4 |
18d | 506.4 | 4 | 40.00 | 3 |
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Ivan, B.-C.; Dumitrascu, F.; Anghel, A.I.; Ancuceanu, R.V.; Shova, S.; Dumitrescu, D.; Draghici, C.; Olaru, O.T.; Nitulescu, G.M.; Dinu, M.; et al. Synthesis and Toxicity Evaluation of New Pyrroles Obtained by the Reaction of Activated Alkynes with 1-Methyl-3-(cyanomethyl)benzimidazolium Bromide. Molecules 2021, 26, 6435. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216435
Ivan B-C, Dumitrascu F, Anghel AI, Ancuceanu RV, Shova S, Dumitrescu D, Draghici C, Olaru OT, Nitulescu GM, Dinu M, et al. Synthesis and Toxicity Evaluation of New Pyrroles Obtained by the Reaction of Activated Alkynes with 1-Methyl-3-(cyanomethyl)benzimidazolium Bromide. Molecules. 2021; 26(21):6435. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216435
Chicago/Turabian StyleIvan, Beatrice-Cristina, Florea Dumitrascu, Adriana Iuliana Anghel, Robert Viorel Ancuceanu, Sergiu Shova, Denisa Dumitrescu, Constantin Draghici, Octavian Tudorel Olaru, George Mihai Nitulescu, Mihaela Dinu, and et al. 2021. "Synthesis and Toxicity Evaluation of New Pyrroles Obtained by the Reaction of Activated Alkynes with 1-Methyl-3-(cyanomethyl)benzimidazolium Bromide" Molecules 26, no. 21: 6435. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216435