Catalyst and solvent-free, ultrasound promoted rapid protocol for the one-pot synthesis of Benzothiazol-2-yl(piperazin-1-yl)methanones: Design, synthesis, X-ray crystallography, In Vitro, and In Silico studies

Green synthesis is acknowledged as a crucial tool in mitigating the detrimental impacts linked to conventional methods of synthesizing organic compounds, which are commonly employed in both laboratory and industrial settings. In this study, a green chemistry approach was utilized for the synthesis of benzothiazol-2-yl(piperazin-1-yl)methanones scaffold, resulting in the synthesis of novel antimycobacterial chemotypes. A total of twelve benzothiazole-2-carboxamide compounds with distinct structural variations were successfully synthesized and subjected to in vitro testing against the Mycobacterium tuberculosis H37Rv strain to evaluate their potential as anti-tubercular agents. All the synthesized compounds were analyzed by FTIR, NMR, and Mass spectral analysis. Structures of 5a, 5g, and 5l were confirmed by single crystal X-ray diffraction. All synthesized compounds displayed potential anti-mycobacterial activity with MICs in the low range. The synthesized compounds were also subjected to evaluation of binding interactions with target protein, and molecular dynamics simulation. The compounds 5a, 5f, 5g, 5h, and 5l have shown significant docking scores i.e., -8.0,-8.9,-9.1,-8.9,-8.8 kcal/mol respectively to interact with tuberculosis protein followed by other compounds with the related targets of DprE1, Polyketide synthase, and Protein kinase B . Thus, the substantial anti-TB of benzothiazole-2-carboxamides (5a-l ) derivatives implies that; these scaffolds could help in assisting the development of lead compounds for the treatment of antitubercular infections.