N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity
| Autor: | Niranjan Thota, Amit Kaushik, Per I. Arvidsson, Gyanu Lamichhane, Thavendran Govender, Anil A. Chuturgoon, Anou M. Somboro, Parameshwar Makam, Naeem Sheik Abdul, Tricia Naicker, Kamal K. Rajbongshi, Hendrik G. Kruger, Savania Nagiah |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
biology
010405 organic chemistry medicine.drug_class Chemistry Pseudomonas aeruginosa Organic Chemistry Antibiotics Mycobacterium abscessus biology.organism_classification Antimycobacterial Antimicrobial medicine.disease_cause 01 natural sciences Biochemistry 0104 chemical sciences Microbiology Mycobacterium tuberculosis 010404 medicinal & biomolecular chemistry Drug Discovery medicine Antibacterial activity Ethambutol medicine.drug |
| Zdroj: | ACS Med Chem Lett |
| Popis: | [Image: see text] Herein we demonstrate the expanded utility of a recently described N-trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel N-trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against Mycobacterium tuberculosis (M. tb.) and Mycobacterium abscessus and Gram + Ve (Streptococcus aureus, Bacillus subtilis), and Gram – Ve (Escherichia coli, Pseudomonas aeruginosa) bacteria. Two compounds, 13 and 15 showed high antimycobacterial activity with MIC value of 4–8 μg/mL; i.e. comparable to WHO recommended first line antibiotic for TB infection ethambutol. The same compounds were also found to be cytotoxic in HepG2 cells (compound 13 IC(50) = 15 μg/mL; compound 15 IC(50) = 65 μg/mL). A structure activity relationship, using matched pair analysis, gave the unexpected conclusion that the trifluoromethylthio moiety was responsible for the cellular and bacterial toxicity. Given the increasing use of the trifluoromethylthio group in contemporary medicinal chemistry, this observation calls for considerations before implementation of the functionality in drug design. |
| Databáze: | OpenAIRE |
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