Pyridine embedded 1,3,4-oxadiazole derivatives: Design, synthesis, molecular docking and antitubercular activity evaluation.

In the present study, a series of new pyridine-embedded 1,3,4-oxadiazole derivatives (OXn series) bearing terminal long-chain alkoxy groups like decyloxy, dodecyloxy, tetra decyloxy, and hexadecyloxy groups have been systematically synthesized. Further, the presence of these long-chain alkoxy groups in the OXn series would help to improve the overall molecular lipophilicity and ability to penetrate the lipid-rich mycobacterial cell membrane. Molecular docking has been performed against the mycobacterial InhA enzyme to gain an insight into the possible interactions with the protein, which could pave the way for our endeavor to identify potent antitubercular candidates. Also, these compounds were evaluated for their in vitro antitubercular activities. Among the screened compounds of OXn series, the compound (OX-14) have exhibited potent antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC value 32.0 μg/mL and ICvalue of 10.4 μg/mL. We believe that further optimization of this molecule may lead to potent antitubercular agents.