Synthesis and bioevaluation of novel 3,4,5-trimethoxybenzylbenzimidazole derivatives that inhibit Helicobacter pylori-induced pathogenesis in human gastric epithelial cells

Helicobacter pylori infection is associated with gastritis, peptic ulcer, and even gastric malignancy. H. pylori's antibiotic resistance is the major obstacle preventing its eradication. A series of 3,4,5-trimethoxybenzylbenzimidazole derivatives were synthesized and evaluated for their anti-H. pylori activity. The compound, 2-fluorophenyl-5-methyl-1-(3,4,5-trimethoxybenzyl)benzimidazole (FMTMB), was determined as the most potent in the inhibition of H. pylori growth and pathogenesis of host cells. An in vitro H. pylori infection model revealed that FMTMB inhibited H. pylori adhesion and invasion of gastric epithelial cells. Results from this study provide evidence that FMTMB is a potent therapeutic agent that exhibits both anti-H. pylori growth properties and anti-H. pylori-induced pathogenesis of cells.

A series of 3,4,5-trimethoxybenzylbenzimidazole derivatives were synthesized. 2-Fluorophenyl-5-methyl-1-(3,4,5-trimethoxybenzyl)benzimidazole (FMTMB) was determined as the most potent in the inhibition of Helicobacter pylori growth and pathogenesis of host cells.Figure optionsDownload as PowerPoint slideHighlights
► A series of 3,4,5-trimethoxybenzylbenzimidazole derivatives were synthesized.
► These compounds possessed anti-Helicobacter pylori (H. pylori) activity.
► FMTMB inhibited H. pylori adhesion and invasion of gastric epithelial cells.
► FMTMB attenuated cytotoxin-associated gene A (CagA)-induced pathogenesis of cells.
► FMTMB attenuated vacuolating cytotoxin A (VacA)-induced cellular vacuolation.