Synthesis, molecular docking, and biological evaluation of novel 1,2,4‐triazole‐isatin derivatives as potential Mycobacterium tuberculosis shikimate kinase inhibitors
| Autor: | Vedika G. Dadlani, Heta Chhabhaiya, Rakesh R. Somani, Pushpendra K. Tripathi |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Isatin
Pharmacology Organic Chemistry Antitubercular Agents Shikimic Acid Microbial Sensitivity Tests Mycobacterium tuberculosis Triazoles Biochemistry Molecular Docking Simulation Phosphotransferases (Alcohol Group Acceptor) Structure-Activity Relationship HEK293 Cells Drug Discovery Humans Tuberculosis Molecular Medicine |
| Zdroj: | Chemical Biology & Drug Design. 100:230-244 |
| ISSN: | 1747-0285 1747-0277 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |