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

doi:10.1016/j.bmcl.2006.12.059

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

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

78 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	1755-1758
Number of pages	4
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	17
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2006.12.059
Publication status	Published - 15 Mar 2007

Access to Document

10.1016/j.bmcl.2006.12.059

https://linkinghub.elsevier.com/retrieve/pii/S0960894X06014776

Cite this

@article{0f9c93bf86514e379c8a741e45c846b5,

title = "N-Caffeoylphenalkylamide derivatives as bacterial efflux pump inhibitors",

abstract = "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.",

author = "Serge Michalet and Gilbert Cartier and Bruno David and Anne-Marie Mariotte and Marie-Genevi{\`e}ve Dijoux-Franca and Kaatz, {Glenn W.} and Michael Stavri and Simon Gibbons",

year = "2007",

month = mar,

day = "15",

doi = "10.1016/j.bmcl.2006.12.059",

language = "English",

volume = "17",

pages = "1755--1758",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

number = "6",

}

N-Caffeoylphenalkylamide derivatives as bacterial efflux pump inhibitors. / Michalet, Serge; Cartier, Gilbert; David, Bruno; Mariotte, Anne-Marie; Dijoux-Franca, Marie-Geneviève; Kaatz, Glenn W.; Stavri, Michael; Gibbons, Simon.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 17, No. 6, 15.03.2007, p. 1755-1758.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - N-Caffeoylphenalkylamide derivatives as bacterial efflux pump inhibitors

AU - Michalet, Serge

AU - Cartier, Gilbert

AU - David, Bruno

AU - Mariotte, Anne-Marie

AU - Dijoux-Franca, Marie-Geneviève

AU - Kaatz, Glenn W.

AU - Stavri, Michael

AU - Gibbons, Simon

PY - 2007/3/15

Y1 - 2007/3/15

N2 - 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.

AB - 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.

U2 - 10.1016/j.bmcl.2006.12.059

DO - 10.1016/j.bmcl.2006.12.059

M3 - Article

VL - 17

SP - 1755

EP - 1758

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 6

ER -