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

Abstract

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: Synthesis and bioactivity screening of a novel series of benzimidazole derivatives. Methods: Nine novel benzimidazole derivatives 10α-Ɣ were synthesized, isolated, and their structures were elucidated by 1H-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 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. Investigate of the cytotoxicity profile of the target compound, showed all 10α-Ɣ have IC50 values higher than 50 µM on tested cell line. Conclusion: The results showed that synthesized benzimidazole derivatives can be highly effective as urease inhibitors.