Development of 1,2,4-Triazole-5-Thione Derivatives as Potential Inhibitors of Enoyl Acyl Carrier Protein Reductase (InhA) in Tuberculosis.

Abstract

Tuberculosis (TB) ranks second, next to AIDS making it most formidable disease in the present age. One of the crucial enzymes involved in cell wall synthesis of Mycobacterium tuberculosis, InhA (enoyl acyl carrier protein reductase), one of the crucial enzymes involved in cell wall synthesis of Mycobacterium tuberculosis, has been authenticated as an effective target for anti-mycobacterial drug development. In the current work, novel derivatives of 1,2,4-triazole-5-thione rationally designed, synthesized and spectrally characterized as promising InhA inhibitors. Anti-mycobacterial potential was determined by resazurin microtiter assay using Mtb H₃₇Rv strain. The mechanism of action of these compounds was confirmed by InhA enzyme inhibition studies. 6b, the most active compound of the series displayed MIC of 0.19 µM in resazurin microtiter assay and InhA inhibition with IC₅₀ of 90 nM.