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

Abstract

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 100μg/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.