Imidazopyridine Hydrazine Conjugates as Potent Anti-TB Agents with their Docking, SAR, and DFT Studies

Novel imidazopyridines hydrazine conjugates were designed and synthesized for their anti-tubercular (anti-TB) activity. A cytotoxicity assay was conducted with Vero cells to determine the safety profile of the most effective compounds. It was found that compound (IA3) (MIC=0.78 mu M) and (IA8) (MIC=1.12 mu M) were nearly 3.7 and 2.5 times more active than pyrazinamide. Based on Density functional theory (DFT), these molecules exhibited better charge transfer between molecular orbital's, which made them suitable for biological applications. Molecular docking on Mycobacterium tuberculosis InhA bound to NITD-916 (PDB: 4R9S) revealed that compounds possessed greater binding affinity towards proteins. In addition, the most active anti-TB compounds (IA3) and (IA8) exhibited high levels of interaction with the target protein and exceptional safety profile, suggesting they may prove to be effective leads for new drugs. Compound (IA3) and (IA8) were nearly 3.7 and 2.5 times more active than standard anti-TB drug pyrazinamide respectively. Docking results showed better interactions between the compounds and their target proteins. Toxicity studies on Vero cells confirmed the nontoxic nature of the compounds. image