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Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors

Murray, Ewan J.; Crowley, Rebecca C.; Truman, Alex; Clarke, Simon R.; Cottam, James A.; Jadhav, Gopal P.; Steele, Victoria R.; O’Shea, Paul; Lindholm, Catharina; Cockayne, Alan; Chhabra, Siri Ram; Chan, Weng C.; Williams, Paul

Authors

Ewan J. Murray

Rebecca C. Crowley

Alex Truman

Simon R. Clarke

James A. Cottam

Gopal P. Jadhav

Victoria R. Steele

Paul O’Shea

Catharina Lindholm

Alan Cockayne

Siri Ram Chhabra

Weng C. Chan

Paul Williams

Abstract

A series of 3-oxo-C12-HSL, tetramic acid, and tetronic acid analogues were synthesized to gain insights into the structural requirements for quorum sensing inhibition in Staphylococcus aureus. Compounds active against agr were noncompetitive inhibitors of the autoinducing peptide (AIP) activated AgrC receptor, by altering the activation efficacy of the cognate AIP-1. They appeared to act as negative allosteric modulators and are exemplified by 3-tetradecanoyltetronic acid 17, which reduced nasal cell colonization and arthritis in a murine infection model.

Journal Article Type Article
Publication Date Mar 27, 2014
Journal Journal of Medicinal Chemistry
Print ISSN 0022-2623
Electronic ISSN 1520-4804
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 57
Issue 6
Institution Citation Murray, E. J., Crowley, R. C., Truman, A., Clarke, S. R., Cottam, J. A., Jadhav, G. P., …Williams, P. (2014). Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors. Journal of Medicinal Chemistry, 57(6), doi:10.1021/jm500215s
DOI https://doi.org/10.1021/jm500215s
Publisher URL http://pubs.acs.org/doi/abs/10.1021/jm500215s
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0




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