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. 2022 Aug;100(2):230-244.
doi: 10.1111/cbdd.14060. Epub 2022 Jun 6.

Synthesis, molecular docking, and biological evaluation of novel 1,2,4-triazole-isatin derivatives as potential Mycobacterium tuberculosis shikimate kinase inhibitors

Vedika G Dadlani  1 , Heta Chhabhaiya  1 , Rakesh R Somani  2 , Pushpendra K Tripathi  3
Affiliations

Synthesis, molecular docking, and biological evaluation of novel 1,2,4-triazole-isatin derivatives as potential Mycobacterium tuberculosis shikimate kinase inhibitors

Vedika G Dadlani et al. Chem Biol Drug Des. 2022 Aug.

Abstract

The issue of emerging resistance to antitubercular drugs has created a formidable barrier in the effective prevention and cure of tuberculosis globally. In an effort to search for new antimycobacterial agents, possibly comprising new pharmacophore, novel triazole-isatin derivatives were designed as Mycobacterium tuberculosis shikimate kinase inhibitors and synthesized by microwave-assisted method. The synthesized molecules were evaluated for their antimycobacterial activity by MABA assay against M. tuberculosis H37Rv. The molecule 5h demonstrated MIC of 0.8 μg/ml and good safety profile with higher selectivity index with HEK293 cell line. The antimycobacterial activity was further substantiated with molecular docking studies. The triazole-isatin derivatives showed significant binding interactions with amino acid residues in the active site of the enzyme. These studies revealed that molecule 5h could act as a potential lead molecule for further studies to find new target-directed molecules.

Keywords: HEK293 cell line; MABA assay; docking; druglikeness; shikimate kinase inhibitor; triazole-isatin.

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