Synthesis of 1,2,3-Triazolo[4,5-h]quinolone Derivatives with Novel Anti-Microbial Properties against Metronidazole Resistant Helicobacter pylori.

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

doi:10.3390/molecules22050841

Abstract

Helicobacter pylori infection can lead to gastritis, peptic ulcer, and the development of mucosa associated lymphoid tissue (MALT) lymphoma. Treatment and eradication of H. pylori infection can prevent relapse and accelerate the healing of gastric and duodenal ulcers as well as regression of malignancy. Due to the increasing emergence of antibiotic resistance among clinical isolates of H. pylori, alternative approaches using newly discovered antimicrobial agents in combination with the standard antibiotic regimens for the treatment of H. pylori are of major importance. The purpose of the present study was to investigate the effect of newly synthesized 8-amino 7-substituted fluoroquinolone and their correspondent cyclized triazolo derivatives when either alone or combined with metronidazole against metronidazole-resistant H. pylori. Based on 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 best in vitro effect for compounds 4b and 4c. Fractional inhibitory concentration (FIC) mean values showed synergistic pattern in all compounds of Group 5. In addition, additive activities of some of the tested compounds of Group 4 were observed when combined with metronidazole. In contrast, the tested compounds showed no significant urease inhibition activity. These results support the potential of new fluoroquinolone derivatives to be useful in combination with anti-H. pylori drugs in the management of H. pylori-associated diseases.

Highlights

H. pylori is a gram negative, spiral shaped, microaerophilic bacterium [1,2]
Eradication of H. pylori has been shown to result in ulcer healing, prevent peptic ulcer recurrence, and reduce the prevalence of gastric cancer in high risk populations [7,8]
Our study showed no significant urease inhibitory effect for compounds 4a, 4b, and 4c at 1000 μg/mL with inhibitory percent 13, 10, and 33%, respectively

Summary

Introduction

Eradication of H. pylori has been shown to result in ulcer healing, prevent peptic ulcer recurrence, and reduce the prevalence of gastric cancer in high risk populations [7,8]. The conventional treatment for eradication therapy of H. pylori allows obtaining high cure. The conventional treatment for eradication therapy of H. pylori allows obtaining high cure rates, rates, the eradication failure rate remains of [12]. This can be explained by lack of patient the eradication failure rate remains of 5–20% [12]. This can be explained by lack of patient compliance compliance with the drug and the development of antibiotic resistance [13,14,15]

Objectives

Methods

Results

Conclusion