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3-Aryl-4-methyl-2-quinolones Targeting Multiresistant Staphylococcus aureus Bacteria

Authors

  • Anne Doléans-Jordheim,

    1. Université Claude Bernard Lyon 1, 69008 Lyon (France)
    2. Research Group on Bacterial Opportunistic Pathogens and Environment, UMR 5557-Ecologie Microbienne Lyon, Université Claude Bernard Lyon 1, CNRS, VetAgro Sup, 69600 Villeurbanne (France)
    3. Hospices Civils de Lyon, 69000 Lyon (France)
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  • Jean-Baptiste Veron,

    1. Université Joseph Fourier, Grenoble I/CNRS, UMR 5063, Département de Pharmacochimie Moléculaire, BP 53, 38401 Grenoble Cedex 9 (France)
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  • Olivier Fendrich,

    1. Université Claude Bernard Lyon 1, 69008 Lyon (France)
    2. Research Group on Bacterial Opportunistic Pathogens and Environment, UMR 5557-Ecologie Microbienne Lyon, Université Claude Bernard Lyon 1, CNRS, VetAgro Sup, 69600 Villeurbanne (France)
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  • Emmanuelle Bergeron,

    1. Université Claude Bernard Lyon 1, 69008 Lyon (France)
    2. Research Group on Bacterial Opportunistic Pathogens and Environment, UMR 5557-Ecologie Microbienne Lyon, Université Claude Bernard Lyon 1, CNRS, VetAgro Sup, 69600 Villeurbanne (France)
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  • Adrien Montagut-Romans,

    1. Université Joseph Fourier, Grenoble I/CNRS, UMR 5063, Département de Pharmacochimie Moléculaire, BP 53, 38401 Grenoble Cedex 9 (France)
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  • Yung-Sing Wong,

    1. Université Joseph Fourier, Grenoble I/CNRS, UMR 5063, Département de Pharmacochimie Moléculaire, BP 53, 38401 Grenoble Cedex 9 (France)
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  • Bianca Furdui,

    1. Université Joseph Fourier, Grenoble I/CNRS, UMR 5063, Département de Pharmacochimie Moléculaire, BP 53, 38401 Grenoble Cedex 9 (France)
    2. Dunarea de Jos University, Department of Chemistry, Domneasca 47, 800008 Galati (Romania)
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  • Jean Freney,

    1. Université Claude Bernard Lyon 1, 69008 Lyon (France)
    2. Research Group on Bacterial Opportunistic Pathogens and Environment, UMR 5557-Ecologie Microbienne Lyon, Université Claude Bernard Lyon 1, CNRS, VetAgro Sup, 69600 Villeurbanne (France)
    3. Hospices Civils de Lyon, 69000 Lyon (France)
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  • Charles Dumontet,

    1. Université Claude Bernard Lyon 1, 69008 Lyon (France)
    2. Hospices Civils de Lyon, 69000 Lyon (France)
    3. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, 69000 Lyon (France)
    4. CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, 69000 Lyon (France)
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    • These authors contributed equally to this work.

  • Ahcène Boumendjel

    Corresponding author
    1. Université Joseph Fourier, Grenoble I/CNRS, UMR 5063, Département de Pharmacochimie Moléculaire, BP 53, 38401 Grenoble Cedex 9 (France)
    • Université Joseph Fourier, Grenoble I/CNRS, UMR 5063, Département de Pharmacochimie Moléculaire, BP 53, 38401 Grenoble Cedex 9 (France)
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    • These authors contributed equally to this work.


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.

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