Design, synthesis, evaluation, and molecular docking study of novel quinoline hydrazone analogues as anti-tubercular agents

Tuberculosis (TB) remains a global health concern, necessitating the continuous search for novel therapeutic agents to combat drug-resistant strains and enhance treatment efficacy. The present study focuses on designing, synthesizing, and exploring quinoline analogues as potential anti-tubercular agents. Quinoline scaffolds like bedaquiline inhibit the ATP synthase enzyme involved in energy production. A diverse library of 19 quinoline derivatives was systematically synthesized through rational structural modifications. The quinoline analogues were evaluated for their anti-tubercular activity against Mycobacterium tuberculosis (M.tb). Furthermore, the study delves into the molecular interactions between the synthesized quinoline derivatives and M.tb ATP synthase, shedding light on the underlying mechanisms of their anti-tubercular activity. The initial in-vitro screening revealed that some of the designed molecules were active against M.tb, making them potential candidates for further development.