Synthesis, biological evaluation, and molecular docking study of pyridine clubbed 1,3,4-oxadiazoles as potential antituberculars

ABSTRACT

A series of pyridine clubbed 1,3,4-oxadiazole derivatives were efficiently synthesized, characterized by standard spectral techniques and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H₃₇Ra and Mycobacterium bovis BCG in active and dormant state using an established methods. Compounds 5a, 5m, and 5t were identified as the most active compounds against MTB. Molecular docking was performed against MTB enoyl-ACP (CoA) reductase (FabI/ENR/InhA) enzyme to predict the binding modes and affinity. The theoretical predictions from molecular docking could establish a link between the observed biological activity and the binding affinity shedding light into specific bonded and non-bonded interactions influencing the activity. The active compounds were studied for cytotoxicity against three cell lines and were found to be non-cytotoxic. Specificity of these compounds was checked by screening them for their antibacterial activity against four bacterial strains.

GRAPHICAL ABSTRACT

KEYWORDS:

• Antibacterial activity
• antituberculosis activity
• cytotoxicity activity

Acknowledgments

Authors are thankful to the Director of NCL Pune for providing biological screening of title compounds. Authors also thank Schrödinger Inc. for providing the Demo license of Schrödinger Molecular modeling suite that has tremendously helped in performing the molecular modeling studies.

Additional information

Funding

Authors are thankful to the University Grants Commission, New Delhi and Department of Science & Technology, New Delhi for financial support under the NON-SAP and DST-FIST programs respectively. Krunalsinh A. Jadeja is thankful to UGC, New Delhi for UGC-MRP Project Fellowship (UGC F. No.-43-164/2014(SR)). Amit R. Trivedi is also thankful to UGC for providing Dr. D. S. Kothari Post-Doctoral Fellowship.