Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors

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 Agr...

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Main Authors: 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
Format: Article
Published: American Chemical Society 2014
Online Access:https://eprints.nottingham.ac.uk/37554/
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author 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
author_facet 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
author_sort Murray, Ewan J.
building Nottingham Research Data Repository
collection Online Access
description 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.
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institution University of Nottingham Malaysia Campus
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last_indexed 2025-11-14T19:32:48Z
publishDate 2014
publisher American Chemical Society
recordtype eprints
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spelling nottingham-375542020-05-04T16:44:14Z https://eprints.nottingham.ac.uk/37554/ 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 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. American Chemical Society 2014-03-27 Article PeerReviewed 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. and Williams, Paul (2014) Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors. Journal of Medicinal Chemistry, 57 (6). pp. 2813-2819. ISSN 1520-4804 http://pubs.acs.org/doi/abs/10.1021/jm500215s doi:10.1021/jm500215s doi:10.1021/jm500215s
spellingShingle 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
Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors
title Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors
title_full Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors
title_fullStr Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors
title_full_unstemmed Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors
title_short Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors
title_sort targeting staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors
url https://eprints.nottingham.ac.uk/37554/
https://eprints.nottingham.ac.uk/37554/
https://eprints.nottingham.ac.uk/37554/