Novel benzimidazole derivatives; synthesis, bioactivity and molecular docking study as potent urease inhibitors

Background Benzimidazole derivatives are widely used to design and synthesize novel bioactive compounds. There are several approved benzimidazole-based drugs on the market. Objectives In this study, we aimed to design and synthesize a series of novel benzimidazole derivatives 8a-n that are urease inhibitors. Methods All 8a-n were synthesized in a multistep. To determine the urease inhibitory effect of 8a-n , the urease inhibition kit was used. The cytotoxicity assay of 8a-n was determined using MTT method. Molecular modelling was determined using autodock software. Results All 8a-n were synthesized in high yield, and their structures were determined using 1 H-NMR, 13 C-NMR, MS, and elemental analyses. In compared to thiourea and hydroxyurea as standards (IC50: 22 and 100 µM, respectively), all 8a-n had stronger urease inhibition activity (IC50: 3.36—10.81 µM). With an IC50 value of 3.36 µM, 8e had the best enzyme inhibitory activity. On two evaluated cell lines, the MTT cytotoxicity experiment revealed that all 8a-n have IC50 values greater than 50 µM. Finally, a docking investigation revealed a plausible way of interaction between the 8e and 8d and the enzyme's active site's key residues. Conclusion The synthesized benzimidazole derivatives exhibit high activity, suggesting that further research on this family of compounds would be beneficial to finding a potent urease inhibitor. Graphical abstract