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Potent antibacterial activity of Y-754, a novel benzimidazole compound with selective action against Helicobacter pylori

Abstract

Y-754, a novel benzimidazole compound, was investigated for in vitro and in vivo antibacterial activity. Unlike amoxicillin, clarithromycin, and metronidazole, the compound had no activity against common aerobic and anaerobic bacteria other than Helicobacter pylori. The minimum inhibitory concentration of Y-754 against H. pylori, at 0.025 µg/ml, was nearly equal to that of amoxicillin and clarithromycin. The respective concentrations of Y-754, amoxicillin, clarithromycin, and metronidazole required to inhibit 90% of 39 isolates of H. pylori were 0.05, 0.39, 6.25, and 25 µg/ml, indicating the potent activity of Y-754, including activity against clarithromycin- and metronidazole-resistant strains. The anti-H. pylori activity of Y-754 was potent even at pH 5.5 and was bactericidal at concentrations of 0.1 µg/ml and above. Exposure of H. pylori to Y-754 did not result in the induction of drug-resistant mutation. Oral administration (10 mg/kg twice a day for 7 days) to Mongolian gerbils infected with strain ATCC 43504 demonstrated that Y-754 was effective in H. pylori eradication and that its eradication efficacy increased in line with the progress of damage to the gastric mucosa caused by H. pylori infection. Y-754 was also efficacious in the treatment of infection by the clarithromycin-resistant strain OIT-36. The results obtained lead to the expectation that the new benzimidazole Y-754 will, in the near future, be used for H. pylori eradication therapy in peptic ulcer patients.

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Correspondence to Eiji Iwao.

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Iwao, E., Yamamoto, K., Yokoyama, Y. et al. Potent antibacterial activity of Y-754, a novel benzimidazole compound with selective action against Helicobacter pylori . J Infect Chemother 10, 90–96 (2004). https://doi.org/10.1007/s10156-004-0299-1

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  • DOI: https://doi.org/10.1007/s10156-004-0299-1

Key words

  • Benzimidazole
  • Antibacterial activity
  • Helicobacter pylori
  • Mongolian gerbil