title: 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 ofHelicobacter pylori. Due to the emergence of antibiotic resistance among clinical strains ofH. pylori, alternative approaches using newly discovered antimicrobial agents in combination with the standard regimens for the treatment ofH. pyloriare 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-resistantH. 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 ofH. pylori, with the best in vitro effect for compound3c. In addition, synergistic and additive activities of some of the tested compounds were observed when combined with metronidazole. Furthermore, among the tested nitroflouroquinolone derivatives, compound3bshowed significant urease inhibition activity with IC50of 62.5 µg/mL. These results suggest that 8-nitroflouroquinolone derivatives may have a useful role in combination with anti-H. pyloridrugs in the management ofH. pylori-associated diseases.
authors.affiliation: Faculty of Pharmacy, University of Petra, 11914 Amman, Jordan. labuqatouseh@uop.edu.jo.
authors.forename: Luay
authors.initials: L
authors.lastname: Abu-Qatouseh
authors.affiliation: Faculty of Pharmacy, University of Jordan,11914 Amman, Jordan. mohammad.abusini@zuj.edu.jo.|Faculty of Pharmacy, Al-Zaytoonah University of Jordan, 11733 Amman, Jordan. mohammad.abusini@zuj.edu.jo.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abu-Sini
authors.affiliation: Faculty of Health Sciences, American University of Madaba, 11821 Madaba, Jordan. a.mayyas@aum.edu.jo.
authors.forename: Amal
authors.initials: A
authors.lastname: Mayyas
authors.affiliation: Faculty of Pharmacy, University of Jordan,11914 Amman, Jordan. hiary@ju.edu.jo.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Al-Hiari
authors.affiliation: Faculty of Pharmacy, University of Jordan,11914 Amman, Jordan. rulad@ju.edu.jo.
authors.forename: Rula
authors.initials: R
authors.lastname: Darwish
authors.affiliation: Faculty of Pharmacy, University of Jordan,11914 Amman, Jordan. aburjai@ju.edu.jo.
authors.forename: Talal
authors.initials: T
authors.lastname: Aburjai
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D037521:Virulence Factors; D008795:Metronidazole; D014510:Urease
keywords: H. pylori; nitrofluoroquinolones; urease inhibition