Discovery, Synthesis, and Optimization of 1,2,4-Triazolyl Pyridines Targeting Mycobacterium tuberculosis.

ABSTRACT: The rise in multidrug resistant tuberculosis cases underscores the urgent need to develop new treatment strategies for tuberculosis. Herein, we report the discovery and synthesis of a new series of compounds containing a 3-thio-1,2,4-triazole moiety that show inhibition of Mycobacterium tuberculosis (Mtb) growth and survival. Structure-activity relationship studies led us to identify several potent analogs displaying low micromolar to nanomolar inhibitory activity, specifically against Mtb. The potent analogs demonstrated no cytotoxicity in mammalian cells at over 100 times the effective concentration required in Mtb and were bactericidal against Mtb during infection of macrophages. In the exploratory ADME investigations, we observed suboptimal ADME chara

SUBMITTER: Berida T 

PROVIDER: S-EPMC10807233 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature