title: 3-Aryl-4-methyl-2-quinolones targeting multiresistant Staphylococcus aureus bacteria.
abstract: The NorA efflux pump lowers intracellular fluoroquinolone concentrations by expelling antibiotics through the membrane of Staphylococcus aureus. We identified 3-aryl-4-methyl-2-quinolin-2-ones as compounds able to restore the activity of the NorA substrate, ciprofloxacin, against resistant S. aureus strains, and acting as efflux pump inhibitors (EPI). In particular, 5-hydroxy-7-methoxy-4-methyl-3-phenylquinolin-2-one (6 c) presents both an EPI and an antimicrobial effect. Its efficacy and safety make it a potential candidate for further investigations.
authors: Université Claude Bernard Lyon 1, 69008 Lyon, France.
authors: Anne
authors: A
authors: Doléans-Jordheim
authors: Jean-Baptiste
authors: JB
authors: Veron
authors: Olivier
authors: O
authors: Fendrich
authors: Emmanuelle
authors: E
authors: Bergeron
authors: Adrien
authors: A
authors: Montagut-Romans
authors: Yung-Sing
authors: YS
authors: Wong
authors: Bianca
authors: B
authors: Furdui
authors: Jean
authors: J
authors: Freney
authors: Charles
authors: C
authors: Dumontet
authors: Ahcène
authors: A
authors: Boumendjel
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002939:Ciprofloxacin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015363:Quinolones; C075040:NorA protein, Staphylococcus