N-Caffeoylphenalkylamide derivatives as bacterial efflux pump inhibitors

Serge Michalet, Gilbert Cartier, Bruno David, Anne-Marie Mariotte, Marie-Geneviève Dijoux-Franca, Glenn W. Kaatz, Michael Stavri, Simon Gibbons

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As part of an ongoing project to identify plant natural products as efflux pump inhibitors (EPIs), bioassay-guided fractionation of the methanolic extract of Mirabilis jalapa Linn. (Nyctaginaceae) led to the isolation of an active polyphenolic amide: N-trans-feruloyl 4′-O-methyldopamine. This compound showed moderate activity as an EPI against multidrug-resistant (MDR) Staphylococcus aureus overexpressing the multidrug efflux transporter NorA, causing an 8-fold reduction of norfloxacin MIC at 292 μM (100 μg/mL). This prompted us to synthesize derivatives in order to provide structure–activity relationships and to access more potent inhibitors. Among the synthetic compounds, some were more active than the natural compound and N-trans-3,4-O-dimethylcaffeoyl tryptamine showed potentiation of norfloxacin in MDR S. aureus comparable to that of the standard reserpine.
Original languageEnglish
Pages (from-to)1755-1758
Number of pages4
JournalBioorganic & Medicinal Chemistry Letters
Issue number6
Publication statusPublished - 15 Mar 2007

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