Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors

Murray, Ewan J. and Crowley, Rebecca C. and Truman, Alex and Clarke, Simon R. and Cottam, James A. and Jadhav, Gopal P. and Steele, Victoria R. and O'Shea, Paul and Lindholm, Catharina and Cockayne, Alan and Chhabra, Siri Ram and Chan, Weng C. and Williams, Paul (2014) Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors. Journal of Medicinal Chemistry, 57 (3). pp. 2813-2819. ISSN 0022-2623

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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.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Medicinal Chemistry
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/3000/3002
Subjects:
?? drug discoverymolecular medicine ??
ID Code:
126033
Deposited By:
Deposited On:
22 Jun 2018 10:18
Refereed?:
Yes
Published?:
Published
Last Modified:
15 Jul 2024 17:59