Development of 1,2,4-triazole-5-thione derivatives as potential inhibitors of enoyl acyl carrier protein reductase (InhA) in tuberculosis.

Document Type: Research article

Authors

Department of Pharmaceutical Chemistry, Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai-400614, Maharashtra, India.

Abstract

Tuberculosis (TB) ranks second, next to AIDS making it most formidable disease if the present age. One of the crucial enzymes involved in cell wall synthesis of Mycobacterium tuberculosis, InhA (enoyl acyl carrier protein reductase) has been authenticated as an effective target for anti-mycobacterial drug development. In the current work, we have developed novel derivatives of 1,2,4-triazole-5-thione as promising InhA inhibitors. We rationally designed these 1,2,4-triazole-5-thione compounds, synthesized and spectrally characterized them. 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. 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.

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