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

Sameer I. Shaikh; Zahid Zaheer; Santosh N. Mokale; Deepak K. Lokwani

doi:10.22159/ijpps.2017v9i11.20469

Authors

Sameer I. Shaikh Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, (M.S.), India
Zahid Zaheer Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, (M.S.), India
Santosh N. Mokale Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, (M.S.), India
Deepak K. Lokwani Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, (M.S.), India

DOI:

https://doi.org/10.22159/ijpps.2017v9i11.20469

Keywords:

Pyrazole, Antitubercular activity, Cytotoxicity, Molecular docking

Abstract

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). Â 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 Î¼M. 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.

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