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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

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

Author(s): Ebrahim Saeedian Moghadam, Abdullah Mohammed Al-Sadi, Meysam Talebi, Massoud Amanlou, Raphael Stoll, Mohsen Amini* and Raid Abdel-Jalil*

Volume 21, Issue 2, 2024

Published on: 21 September, 2022

Page: [297 - 304] Pages: 8

DOI: 10.2174/1570180819666220811145303

Price: $65

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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: 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 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 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 cytotoxicity 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.

Keywords: Benzimidazole, drug design, helicobacter pylori, heterocyclic chemistry, synthesis, urease inhibitor.

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