Design, synthesis, characterization, in-silico and in-vitro evaluation of novel 2-mercapto benzimidazole derivatives tethered with isoniazid for the treatment of tuberculosis

Abstract 2-Mercapto benzimidazole derivatives are well-recognized for their diverse pharmacological activities, including anti-tubercular, antimicrobial, anti-ulcer, analgesic, and anticancer properties. Isoniazid, a first-line antitubercular agent, has been extensively used in the treatment of Mycobacterium tuberculosis infections. Based on these insights, the present study aimed to design and synthesize novel 2-mercapto benzimidazole derivatives tethered with isoniazid to explore their potential as anti-tubercular agents. An in-silico approach was employed to evaluate the binding efficiency of the designed molecules with key mycobacterial targets. The top-scoring compounds from molecular docking studies were selected for synthesis. Three compounds were successfully synthesized via condensation and acetylation reactions. Structural confirmation of the synthesized compounds was carried out using FT-IR, H1-NMR, and mass spectrometry. The anti-tubercular activity of the synthesized derivatives was assessed using the agar well diffusion method against Mycobacterium tuberculosis. The results demonstrated that the synthesized compounds exhibited noteworthy anti-tubercular activity, comparable to or exceeding that of isoniazid, indicating their potential as promising lead molecules for further development. Graphical abstract