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

Abstract

A series of 3-oxo-C 12 -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. © 2014 American Chemical Society.

Citation

Murray, E. J., Crowley, R. C., Truman, A., Clarke, S. R., Cottam, J. A., Jadhav, G. P., Steele, V. R., O’Shea, P., Lindholm, C., Cockayne, A., Chhabra, S. R., Chan, W. C., & Williams, P. (2014). Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors. Journal of Medicinal Chemistry, 57(6), 2813-2819. https://doi.org/10.1021/jm500215s

• Journal Article Type: Article
• Acceptance Date: Mar 1, 2014
• Online Publication Date: Mar 13, 2014
• Publication Date: Mar 27, 2014
• Deposit Date: Oct 13, 2016
• Publicly Available Date: Oct 13, 2016
• 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
• Pages: 2813-2819
• DOI: https://doi.org/10.1021/jm500215s
• Public URL: https://nottingham-repository.worktribe.com/output/724269
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/jm500215s