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Targeting Staphylococcus aureus quorum sensing with non-peptidic small molecule inhibitors

Murray, E., Crowley, R., Truman, A., Clarke, S., Cottam, J., Jadhav, G., Steele, V., O'Shea, P., Lindholm, C., Cockayne, A., Chhabra, R., Chan, W. C. and Williams, P. (2014) Targeting Staphylococcus aureus quorum sensing with non-peptidic small molecule inhibitors. Journal of Medicinal Chemistry, 57 (6). pp. 2813-2819. ISSN 0022-2623

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To link to this item DOI: 10.1021/jm500215s

Abstract/Summary

A series of 3-oxo-C12-HSL, tetramic acid and tetronic acid analogues was synthesized to gain insights into the structural requirements for quorum sensing inhibition in Staphylococcus aureus. Compounds active against agr were non-competitive inhibitors of the auto-inducing 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.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:36166
Publisher:American Chemical Society

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