Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2813-2819
Number of pages7
JournalJournal of Medicinal Chemistry
Volume57
Issue number6
DOIs
StatePublished - Mar 27 2014
Externally publishedYes

Fingerprint

Quorum Sensing
Staphylococcus aureus
Peptides
Nose
Arthritis
Acids
Infection
N-(3-oxododecanoyl)homoserine lactone
tetramic acid
tetronic acid

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Murray, E. J., Crowley, R. C., Truman, A., Clarke, S. R., Cottam, J. A., Jadhav, G., ... 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

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; Steele, Victoria R.; O'Shea, Paul; Lindholm, Catharina; Cockayne, Alan; Chhabra, Siri Ram; Chan, Weng C.; Williams, Paul.

In: Journal of Medicinal Chemistry, Vol. 57, No. 6, 27.03.2014, p. 2813-2819.

Research output: Contribution to journalArticle

Murray, EJ, Crowley, RC, Truman, A, Clarke, SR, Cottam, JA, Jadhav, G, Steele, VR, O'Shea, P, Lindholm, C, Cockayne, A, Chhabra, SR, Chan, WC & Williams, P 2014, 'Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors', Journal of Medicinal Chemistry, vol. 57, no. 6, pp. 2813-2819. https://doi.org/10.1021/jm500215s
Murray, Ewan J. ; Crowley, Rebecca C. ; Truman, Alex ; Clarke, Simon R. ; Cottam, James A. ; Jadhav, Gopal ; 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. In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 6. pp. 2813-2819.
@article{fa6c8f72c7a44566a933ca54f477e4d2,
title = "Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors",
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.",
author = "Murray, {Ewan J.} and Crowley, {Rebecca C.} and Alex Truman and Clarke, {Simon R.} and Cottam, {James A.} and Gopal Jadhav and Steele, {Victoria R.} and Paul O'Shea and Catharina Lindholm and Alan Cockayne and Chhabra, {Siri Ram} and Chan, {Weng C.} and Paul Williams",
year = "2014",
month = "3",
day = "27",
doi = "10.1021/jm500215s",
language = "English (US)",
volume = "57",
pages = "2813--2819",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "6",

}

TY - JOUR

T1 - Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors

AU - Murray, Ewan J.

AU - Crowley, Rebecca C.

AU - Truman, Alex

AU - Clarke, Simon R.

AU - Cottam, James A.

AU - Jadhav, Gopal

AU - Steele, Victoria R.

AU - O'Shea, Paul

AU - Lindholm, Catharina

AU - Cockayne, Alan

AU - Chhabra, Siri Ram

AU - Chan, Weng C.

AU - Williams, Paul

PY - 2014/3/27

Y1 - 2014/3/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84897442807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897442807&partnerID=8YFLogxK

U2 - 10.1021/jm500215s

DO - 10.1021/jm500215s

M3 - Article

C2 - 24592914

AN - SCOPUS:84897442807

VL - 57

SP - 2813

EP - 2819

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 6

ER -