Nayak, N.Ramprasad, J.Udayakumar, U.2026-02-052015Bioorganic and Medicinal Chemistry Letters, 2015, 25, 23, pp. 5540-55450960894Xhttps://doi.org/10.1016/j.bmcl.2015.10.057https://idr.nitk.ac.in/handle/123456789/26183With the aim of developing promising antitubercular and antibacterial leads, we have designed and synthesized a new series of isonicotinohydrazide based pyrazole derivatives (5a-r). All new derivatives (4a-b and 5a-r) were screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H<inf>37</inf>Rv (MTB) strain. Four compounds 5j, 5k, 5l and 4b emerged as promising antitubercular agents with MIC of ?4.9 ?M which is much lower than the MIC of the first line antitubercular drug, ethambutol. The 3-chlorophenyl substituent at position-3 of the pyrazole ring enhanced the antiTB activity of the molecules. Three derivatives 5b, 5k and 4b exhibited promising antibacterial activity against the tested bacterial strains. The active molecules were nontoxic to normal Vero cells and showed high selectivity index (>160). The structure and antitubercular activity relationship was further supported by in silico molecular docking study of the active compounds against enoyl acyl carrier protein reductase (InhA) enzyme of M. tuberculosis. © 2015 Published by Elsevier Ltd.acyl carrier proteinenoyl acyl carrier protein reductase (NADH)ethambutolisoniazidoxidoreductasepyrazolepyrazole derivativetuberculostatic agentantiinfective agentanimal cellantibacterial activityArticlebacterial straincomputer modelcontrolled studydrug designdrug synthesisin vitro studyminimum inhibitory concentrationmolecular dockingMycobacterium tuberculosisnonhumanstructure activity relationVero cell linebacteriumbinding sitechemical structurechemistrydrug effectsIC50microbial sensitivity testmolecular modelsynthesisAnti-Bacterial AgentsAntitubercular AgentsBacteriaBinding SitesDrug DesignInhibitory Concentration 50IsoniazidMicrobial Sensitivity TestsModels, MolecularMolecular Docking SimulationMolecular StructurePyrazoles