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

• Published in: Chemical biology & drug design Vol. 100; no. 2; pp. 230 - 244
• Main Authors: Dadlani, Vedika G., Chhabhaiya, Heta, Somani, Rakesh R., Tripathi, Pushpendra K.
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.08.2022
• Subjects: Biochemistry & Molecular Biology; Chemistry, Medicinal; docking; druglikeness; HEK293 cell line; Life Sciences & Biomedicine; MABA assay; Pharmacology & Pharmacy; Science & Technology; shikimate kinase inhibitor; triazole‐isatin; TARGET; DESIGN; ACID; triazole-isatin; MECHANISM; HEK293 cell line; MABA assay; PREDICTION; docking; druglikeness; shikimate kinase inhibitor; PATHWAY; BINDING
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.14060

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. Novel triazole‐isatin derivatives were designed as Mycobacterium tuberculosis shikimate kinase inhibitors and synthesized by microwave‐assisted method. Compound 5h demonstrated MIC of 0.8 μg/ml in MABA assay and good safety profile with high selectivity index with HEK293 cell line.