Synthesis of Novel 5‐Oxo‐1,2,4‐Oxadiazole Derivatives as Antitubercular Agents and Their Molecular Docking Study toward Enoyl Reductase (InhA) Enzyme

Abstract

AbstractAn analogue of novel 3‐(1‐(4‐(benzoyl) benzyl)‐1H‐indol‐5‐yl)‐1,2,4‐oxadiazol‐5(4H)‐ones were synthesized in good yields (80–90 %), and its anti‐tubercular (anti‐TB) activity was investigated. All synthesized compounds (7 a–u) showed significant deterioration in the proliferation of the Mycobacterium tuberculosis H37Rv strain. A structure‐activity relationship (SAR) study was performed to identify compounds with mixed anti‐tubercular profiles. These compounds′ minimum inhibitory concentration (MIC) ranged between 0.78 and 25 μg/mL, comparable to standard drugs such as Ethambutol. Moreover, the derivative (7 l) (MIC of 0.78 μg/mL), amongst other 5‐oxo‐1,2,4‐oxadiazole, conferred anti‐TB activity more efficiently than Ethambutol (MIC of 1.56 μg/mL) when tested against all bacterial strains. Additionally, molecular docking studies were used against the mycobacterial enoyl reductase (InhA) enzyme to understand the binding modes of the potent compounds (7 l) and (7 m). Also evaluated were these molecules for in silico ADMET and drug similarity features. Thus, this study identified novel 5‐oxo‐1,2,4‐oxadiazoles as potential targets against tuberculosis. Further optimization of the molecule (7 l) could increase potency and aid in creating newer and better targets against M. tuberculosis.