Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents

5 years ago

Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents

Navnath D. Rode, Anjali P. Likhite, Dhiman Sarkar, Laxman Nawale, Rohini R. Joshi, Amol D. Sonawane, Ramesh A. Joshi

Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 μg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection. A series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra. Triazole thiones showed high antitubercular activity against the dormant stage of M. tuberculosis H37Ra. These compounds were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 µg/ml against THP-1, A549, and PANC-1 human cancer cell lines.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.12939