SYNTHESIS AND EVALUATION OF ANTITUBERCULAR ACTIVITY OF 1, 3, 4-OXADIAZOLE DERIVATIVES

Objective: The present study aimed to design, synthesize, and evaluate two novel series of 1,3,4-oxadiazole derivatives for their antitubercular activity against Mycobacterium tuberculosis H37Rv, supported by molecular docking and absorption, bio-distribution, metabolism, and excretion (ADME) predictions to identify potential lead molecules. Methods: Two series of oxadiazole derivatives2-(3-phenoxybenzylideneamino)-5-(4-substituted phenyl)-1,3,4-oxadiazoles (Series 1a-1e) and N-[5- (4-substituted phenyl)-1,3,4-oxadiazol-2-yl]-5-oxo-1-phenylpyrrolidine-3-carboxamides (Series2a-2e)were synthesized and structurally confirmed using melting point analysis, Ultraviolet-Visible, IR, ¹H-NMR, and mass spectrometry. Antitubercular activity was assessed using the Alamar Blue Assay against M. tuberculosis H37Rv, with isoniazid (INH) as the standard. Molecular docking studies were performed against Enoyl-Acyl Carrier Protein Reductase (InhA), and ADME properties were predicted using an online computational server. Results: Docking studies indicated strong binding affinities for compounds 1e and 2c, with docking scores of −10.7 and −10.5, respectively, suggesting potent interaction with InhA. ADME analysis showed that most derivatives possessed favorable drug-like properties, although compounds 1c and 1d exhibited Lipinski’s rule violations. Biological screening revealed that compound 2b demonstrated the most significant antitubercular activity, with a minimum inhibitory concentration of 1.6 μg/mL compared with the standard drug INH. Conclusion: The synthesized oxadiazole derivatives exhibited moderate to strong antitubercular activity, supported by promising docking scores and acceptable ADME properties. These findings identify derivatives such as 2b as potential leads for further optimization and development of novel antitubercular agents.