ADME, Synthesis and Antimycobacterial Activity of 1,2,4-Triazol-3-thiol Linked Phenylacetamide Derivatives

Abstract

Background:: Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is one of the most contagious and fatal human pathogens which necessitates the development of modified existing drugs or derivatives with action against novel targets. Aims and Objectives:: In the present work, we have explored a few, 2-(5-(substituted)-4H-1,2,4-triazole-2-ylthio)-N-(substituted) phenyl acetamide (5A-5E) derivatives as anti-TB. Materials and Methods:: On the basis of SAR were synthesized and screened against Mycobacterium tuberculosis H37Rv using MABA assay. Their ADME properties were also checked. Results:: ADME analysis showed results comparable with standard drug (rifampicin). Derivative 5D turned out to be the most active amongst all the derivatives with MIC of 0.8μg/ml, comparable to standard drugs like rifampicin(0.8μg/ml) and streptomycin(0.8μg/ml). Conclusion:: All five compounds have shown excellent inhibitory activity (1.6μg/ml) against the Mycobacterium tuberculosis H37Rv strain. Compound 5D shows a promising activity (0.8μg/ml) as compared to standard drugs and also it has shown the highest docking score. Literature search has revealed the presence of 1,2,4-triazole derivatives linked to aromatic link and possessing amide linkage and the presence of Sulphur atom in the most active derivatives, which supports our designed compounds. Based on these findings, further derivatives would be synthesized and explored for their role in tuberculosis.