Alzahrani, Abdullah Yahya AbdullahAdalat, BushraUllah, HayatTaha, MuhammadOthman, Mohamed SFareid, Mohamed AKhaled, Azza MRahim, Fazal2023-10-302023-10-302023-10https://doi.org/10.1016/j.molstruc.2023.136850http://repository.msa.edu.eg/xmlui/handle/123456789/5757The nickel-containing urease enzyme is responsible for the pathogenesis of hepatic coma, hepatic encephalop- athy, urolithiasis, gastric and peptic ulcer. These enzymes also have a negative effect on the efficacy of soil nitrogen to produce crops. The urease enzyme inhibitors may be thought as a strategy for reducing the negative effects of ureolytic bacteria. The present study involves a novel approach to the synthesis benzimidazole thio- semicarbazides and sulphonamide derivatives as potent urease inhibitor. All the analogues exhibited good in- hibition potential. Among the thiosemicarbazides series, the most potent were analogs 1 g and 1 h having an IC50 = 2.40 ± 0.10 and 3.10 ± 0.10 µM respectively. Among the sulphonamide series, the most potent analogs were 2f and 2j having an IC50 = 3.90 ± 0.10 and 1.40 ± 0.001 µM respectively. Structure activity relationship study shows that among the two series, the most potent analogs were those having electron-withdrawing groups. Molecular docking study was carried out to check the interactions between the synthesized compounds and the urease enzyme’s active sites. Furthermore, to evaluate the stability of the most active compound in complex with the urease enzyme a total of 200 ns MD simulation was carried out. The MD simulation study revealed that the compound formed a more stable complex with the urease enzyme and remained stable throughout the 200 ns MD simulation. All Compounds were verified for cytotoxicity against 3T3 mouse fibroblast cell line and detected nontoxic.enSynthesisBenzimidazole analogsUrease activitySARMolecular dockingArticlehttps://doi.org/10.1016/j.molstruc.2023.136850