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

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.

Novel in vitro and in vivo anti-Helicobacter pylori effects of pomegranate peel ethanol extract

“…The clinical strains were isolated from gastric biopsy samples obtained by a gastroenterologist at the Jordan University Hospital during a routine endoscopy. Gastric biopsies were processed according to standard methodology [8]. Briefly, each biopsy was homogenized using a tissue homogenizer (IKA, Staufen, Germany).…”

“…The growth of H. pylori was confirmed according to biochemical tests (positive for oxidase, catalase, and urease). H. pylori cultures were stored at −70°C in trypticase soy broth (Oxoid, Hampshire, UK) containing 10% (v/v) fetal calf serum (PAA, Pasching, Austria) and 15% glycerol [1,8]. All experiments were performed in triplicates to ensure consistency of the results.…”

“…The disk diffusion method was used to study the susceptibility of H. pylori to PPEE. The H. pylori suspension was prepared and adjusted to 6×10 8 CFU/mL (2 McFarland) in a fixed volume of 100 µL as described by Tayseer et al [1] and Abu-Sini et al [8]. The bacterial suspension was cultured on solid Columbia blood agar media.…”

Aryl Diazonium Salt‐Triggered Cyclization and Cycloaddition Reactions: Past, Present, and Future

“…[ 111‐113 ] Importantly, this synthetic strategy was commonly employed in medicinal chemistry, accessing a broad array of biologically active, densely functionalized N 1 ‐substituted benzotriazoles. [ 114‐120 ]…”

Recent advances in design of new urease inhibitors: A review

“…Their two popular representatives – Levofloxacin and Ciprofloxacin (compounds 9 and 10 , Fig. 4 ) [53] , [54] , as well as their analogs [55] , appeared to be quite promising inhibitors of Helicobacter pylori and Proteus mirabilis enzymes. Molecular modeling suggests their binding with carboxylic group interacting with active site nickel ions.…”