Novel 5-fluoro-6-(4-(2-fluorophenyl)piperazin-1-yl)-2-(4-(4-methylpiperazin-1- yl)phenyl)-1H-benzo[d]imidazole Derivatives as Promising Urease Inhibitors

Background Highly pathogenic bacteria colonize and maintain themselves with the aid of an enzyme called urease. Consequently, inhibiting urease enzymes can be a promising method for preventing ureolytic bacterial infections. Objective This study aimed at synthesizing and screening a novel series of benzimidazole derivatives. Methods Nine novel benzimidazole derivatives 10 alpha-were synthesized and isolated. Their structures were elucidated by H-1-NMR and IR spectroscopic techniques besides HRMS. The urease inhibition activity of these compounds was evaluated using the standard urease enzyme inhibition kit. An MTT assay was performed on the NIH-3T3 cell line to investigate the cytotoxicity profile. Results All benzimidazoles 10 alpha-exhibited higher urease inhibition activity (3.06-4.40 mu M) than the reference standards thiourea and hydroxyurea (IC50: 22 and 100 mu M, respectively). 10-1 and 10 alpha-1 exhibited the best activity with the IC50 values of 3.06 and 3.13 mu M, respectively. Investigation of the cytotoxicity profile of the target compound showed that all 10 alpha-have IC50 values higher than 50 mu M on the tested cell line. Conclusion The results showed that synthesized benzimidazole derivatives could be highly effective as urease inhibitors.