Abstract
BACKGROUND: Development of new effective drugs against multidrug resistant Mycobacterium tuberculosis is the need of the hour to combat tuberculosis (TB) disease. MATERIALS AND METHODS: Pyridine-4-carbohydrazide and substituted pyrazole aldehydes were used to synthesize target molecules (6a-r) which were evaluated against H(37)Rv and drug-resistant TB strains. Time kill kinetics assay was performed to check bactericidal/bacteriostatic effect, molecular docking, dynamics simulation over 100 ns was performed against enoyl acyl carrier protein reductase (InhA) along with QSAR, ADMET profile prediction. RESULTS: All compounds displayed excellent MICs in the range of 0.125-16 µg/mL. The most potent compound, 6q, with an MIC of 0.125 µg/mL showed bactericidal effect and was effective on ethambutol and streptomycin resistant Mtb strains with an MIC of 0.03 µg/mL and rifampicin resistant Mtb strain with an MIC of 0.25 µg/mL. CONCLUSION: The pyrazole clubbed with pyridine-4-carbohydrazide is a potential scaffold for further exploration as anti-TB agent.