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 Inhib-itors

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 10α-Ɣ were synthesized and isolated. Their structures were elucidated by¹H-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 10α-Ɣ exhibited higher urease inhibition activity (3.06–4.40 µM) than the reference standards thiourea and hydroxyurea (IC₅₀: 22 and 100 µM, respectively). 10Ɣ-1 and 10α-1 exhibited the best activity with the IC₅₀ values of 3.06 and 3.13 µM, respectively. Investigation of the cyto-toxicity profile of the target compound showed that all 10α-Ɣ have IC₅₀ values higher than 50 µM on the tested cell line. Conclusion: The results showed that synthesized benzimidazole derivatives could be highly effective as urease inhibitors.