Synthesis, Urease Inhibitory Activity, Molecular Docking, Dynamics, MMGBSA and DFT Studies of Hydrazone‐Schiff Bases Bearing Benzimidazole Scaffold

Abstract In this study, eleven hydrazone‐Schiff bases bearing benzimidazole moiety were synthesized successfully via three step reactions and structures of these products were deduced by HR‐ESI‐MS, 1H‐, and 13C‐NMR spectroscopic techniques. Lastly, these derivatives were tested for their in vitro urease inhibitory potential. Six compounds among the series attributed excellent inhibition with IC50 values of 7.20±0.59 to 19.61±1.10 μM better than the reference drug thiourea (IC50=22.12±1.20 μM). Similarly, three derivatives showed significant while two compounds showed less inhibitory effects against the urease enzyme. The molecular docking analysis was carried out to reveal the binding modes and types of interaction taking place between protein (urease) and synthesized compounds. The Density Functional Theory (DFT) calculations were performed at B3LYP/6‐311++G(d,p) to check the structure stability. For the account of intramolecular interaction, the DFT−D3 and Reduced Density Gradient (RDG) analysis were performed. Furthermore, the chemical nature of all compounds was explored by TD‐DFT method using CAM−B3LYP functional with 6–311++G(d,p) basis set. The dynamic simulation as well as MMGBSA studies validated the binding affinity and stability of the ligand receptor complex, displaying main interactions contributing in the biological activity of the product derivatives.