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

Luay Abu-Qatouseh,Amal Mayyas,Talal Aburjai,Yusuf Al-Hiari,Mohammad Abu-Sini,Rula Darwish

doi:10.3390/molecules22010071

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.

Highlights

Helicobacter pylori has been increasingly emerging as a major cause of chronic gastritis and peptic ulcer worldwide [1,2]
Our work showed that significant urease inhibition effect was reported only for compounds 3b and 3c, with higher inhibitory effect for 3c with IC50 value of 62.5 μg/mL (Table 4)
Reagents, and solvents were of analytical grade and used directly without further purification. p-anisidine and p-toluidine were purchased from Fluka (Buchs, Switzerland)

Summary

Introduction

Helicobacter pylori has been increasingly emerging as a major cause of chronic gastritis and peptic ulcer worldwide [1,2]. The eradication of H. pylori and/or attenuating its associated virulence factors can contribute to improving the clinical conditions of patients infected with this bacterium, including the acceleration of peptic ulcer healing and minimizing the recurrence of gastric cancer [6]. Current approaches for the effective eradication of H. pylori include the use of at least two antibiotics and a proton pump inhibitor (triple and more recently quadruple therapy) [7,8]. Due to the emergence of antibiotic resistance among H. pylori clinical strains— against metronidazole and clarithromycin—higher rates of treatment failure of triple therapy have been reported [9,10].

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Conclusion