Design, molecular docking and synthesis of novel 5,6-dichloro-2-methyl-1H-benzimidazole derivatives as potential urease enzyme inhibitors

Abstract

A novel series of 5,6-dichloro-2-methyl-1H-benzimidazole derivatives was synthesized and then screened for their urease inhibitory activity. All compounds showed more potent inhibitory activity in the range of IC50= 0.0294 +/- 0.0015-0.1494 +/- 0.0041 mu M than thiourea (IC50= 0.5117 +/- 0.0159 mu M), as a reference inhibitor. Among all the tested compounds, the compound 15 (IC50= 0.0294 +/- 0.0015 mu M) having strong electron-withdrawing nitro group on the phenyl ring was recorded as the most potent inhibitor of urease. All compounds were docked at the active sites of the Jack bean urease enzyme to investigate the reason of the inhibitory activity and the possible binding interactions of enzyme-ligand complexes.