Biological Evaluation of Lead Benzoic Acid-Based Urease Inhibitors Against Helicobacter Pylori: Cytotoxicity and Antibiotic Synergism
Year: 2026
Type: article
Abstract: Helicobacter pylori remains one of the leading causes of chronic gastritis, peptic ulcer disease, and gastric cancer, while the increasing prevalence of antibiotic-resistant strains has significantly reduced the success of conventional eradication therapies. The present study aimed to investigate the biological potential of lead Benzoic Acid-based urease inhibitors by evaluating their antimicrobial activity against H. pylori, cytotoxicity toward mammalian cell lines, and synergistic interactions with clinically used antibiotics. Lead compounds identified from our previous urease inhibition study were assessed against H. pylori ATCC 43504 using the broth microdilution method to determine minimum inhibitory concentration (MIC) values. Cytotoxicity was evaluated by the MTT assay using Vero, HepG2, and A549 cell lines, and selectivity indices (SI) were calculated to assess therapeutic safety. Drug interaction studies were performed by checkerboard microdilution assay with clarithromycin, amoxicillin, and metronidazole. Among the synthesized derivatives, UI-18 exhibited the most potent antibacterial activity (MIC = 1.56 μg/mL) together with the highest selectivity index (SI = 200.3), indicating excellent antibacterial efficacy with minimal mammalian cytotoxicity. Compounds UI-07, UI-14, and UI-19 also demonstrated strong anti-H. pylori activity and favourable safety profiles. Checkerboard analysis revealed significant synergism between UI-18 and clarithromycin (FICI = 0.38), whereas other antibiotic combinations showed indifferent but non-antagonistic interactions. Overall, the findings demonstrate that Benzoic Acid-based urease inhibitors possess promising anti-H. pylori activity, favourable cellular safety, and the potential to enhance conventional eradication therapy through antibiotic synergism. These results support further optimization and preclinical development of Benzoic Acid derivatives as adjunctive therapeutics for the management of H. pylori infection.
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7172454594