DEVELOPMENT OF NEW PYRAZOLE HYBRIDS AS ANTITUBERCULAR AGENTS: SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY

Objective: synthesis of new 1, 3-diphenyl pyrazole derivatives 9(a-f) and 10(a-f) using molecular hybridization approach for antitubercular and cytotoxic studies.Methods: The structures of synthesized compounds were confirmed by 1H-NMR, 13C-NMR and mass spectra’s. The antitubercular activity of compounds and standard drugs were assessed against Mycobacterium tuberculosis using microplate Alamar Blue assay (MABA). The cytotoxic activities were performed by Sulforhodamine B (SRB) assay. The molecular docking and in silico ADME prediction were studied by using Schrodinger.Results: The results reveals that the compounds 9c, 9d, 10c and 10d exhibited substantial antitubercular potential with MIC < 20 μM. The cytotoxic studies revealed that the active compounds (9d, 10a, and 10d) are non-toxic to HeLa cancer cell lines with selectivity index >10. The molecular docking study was performed to study the binding orientation and affinity of synthesized compounds for InhA enzyme.Conclusion: The study explored that the 1, 3-diphenyl pyrazole hybrids coupled with well known antitubercular drugs could be a potential lead for antitubercular agents. In-silico molecular docking study helps to identify their corresponding intermolecular ligand-protein interactions with target enzyme. Also ADME prediction studies revealed that the compounds were in acceptable range to have pharmacokinetic parameters.