Synthesis of New Nitrofluoroquinolone Derivatives with Novel Anti-Microbial Properties against Metronidazole Resistant H. pylori

Abstract

One of the major therapeutic approaches to preventing relapse and accelerating the healing of duodenal and gastric ulcers is the eradication of Helicobacter pylori. Due to the emergence of antibiotic resistance among clinical strains of H. pylori, alternative approaches using newly discovered antimicrobial agents in combination with the standard regimens for the treatment of H. pylori are increasingly needed. The purpose of the present study was to investigate the effect of newly synthesized 8-nitroflouroqunolone derivatives when used either alone or when combined with metronidazole against metronidazole-resistant H. pylori. Based on the standard antimicrobial susceptibility testing methods and checkerboard titration assay, all of the tested compounds showed interesting antimicrobial activity against 12 clinical strains of H. pylori, with the best in vitro effect for compound 3c. In addition, synergistic and additive activities of some of the tested compounds were observed when combined with metronidazole. Furthermore, among the tested nitroflouroquinolone derivatives, compound 3b showed significant urease inhibition activity with IC50 of 62.5 µg/mL. These results suggest that 8-nitroflouroquinolone derivatives may have a useful role in combination with anti-H. pylori drugs in the management of H. pylori-associated diseases.

Keywords

• nitrofluoroquinolones
• H. pylori
• urease inhibition