Design and Molecular Docking Analysis of Isoniazid-Coupled 5,1H-Tetrazole as Potential Anti-Tubercular Agents Using PyRx and AutoDock (MGLTools-1.5.7)

This study presents the rational design and in silico evaluation of novel isoniazid-linked 5,1H-tetrazole derivatives as potential inhibitors of Mycobacterium tuberculosis. A total of 63 hybrid molecules combining isoniazid and 5,1H-tetrazole moieties were designed using ChemSketch and energy-minimized using the MM2 force field in Biovia Discovery Studio Visualizer. The optimized structures were then docked against the InhA enzyme (PDB IDs: 5JFO and 4QXM), a key target involved in mycolic acid biosynthesis, using AutoDock (MGLTools 1.5.7) and validated through PyRx software. The docking studies employed the Lamarckian Genetic Algorithm to evaluate binding affinities and interactions. Results demonstrated that all designed ligands effectively interacted with the InhA active site. One compound exhibited the strongest binding affinity of −10.6 kcal/mol, establishing stable hydrogen bonds with key residues. Overall, docking scores ranged from −7.8 to −13.464 kcal/mol, indicating favorable interaction profiles.These findings highlight the potential of isoniazid-coupled 5,1H-tetrazoles as promising lead candidates for further development into anti-tubercular agents. Future experimental validation is warranted to confirm their biological efficacy.