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Fundam Clin Pharmacol ; 36(6): 1066-1082, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35475507

RESUMEN

In recent years, bacterial resistance to traditional drugs has increased, and the need to find new effective antibiotics to treat infections caused by multidrug-resistant bacteria has consequently become more important. The current study aimed to evaluate the potentiation of antibiotic activity and efflux pumps inhibition by (2E)-1-(4-aminophenyl)-3-(4-fluorophenyl)prop-2-en-1-one (PA-Fluorine) against the standard and resistant bacterial strains of Staphylococcus aureus and Escherichia coli. The association between PA-Fluorine and ampicillin reduced the minimum inhibitory concentration (MIC), showing a synergistic effect against S. aureus. For E. coli, PA-Fluorine did not show any significant results when associated with ampicillin. Ciprofloxacin and chlorpromazine showed synergy with PA-Fluorine on the two studied strains. An efflux pump mechanism was involved in the mechanism of action of chlorpromazine, norfloxacin, and ethidium bromide. PA-Fluorine synergistically modulated norfloxacin and bromide. It was thus concluded that PA-Fluorine has the potential to enhance antibacterial activity when combined with antibiotics. Molecular docking studies showed the effect of intermolecular interactions of PA-Fluorine on the NorA and MepA efflux pumps. Physicochemical and pharmacokinetic properties were also obtained by ADMET studies for this chalcone, which presents be a strong candidate as an efflux pump inhibitor.


Asunto(s)
Antibacterianos , Simportadores , Ampicilina/farmacología , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Clorpromazina/farmacología , Escherichia coli/metabolismo , Flúor/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Norfloxacino/farmacología , Staphylococcus aureus , Simportadores/metabolismo
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