Journal of Medicinal Chemistry

, volume 60 , issue 1 , pages 215-227

Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa

July Fong ^{1, 2}

Mingjun Yuan ¹

Tim Holm Jakobsen ³

Kim T Mortensen ⁴

May Margarette Salido Delos Santos ¹

Song Lin Chua ¹

Liang Yang ^{1, 2}

Choon Hong Tan ^{1, 5}

Thomas E Nielsen ^{1, 3}

Michael Givskov ^{1, 3}

Hide authors affiliations Show authors affiliations: 5 affiliations

Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore |

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore |

Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 København N, Denmark |

⁴

Department of Chemistry, Technical University of Denmark, Kemitorvet, 2800 Kgs Lyngby, Denmark |

⁵

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore |

Publication type: Journal Article

Publication date: 2016-12-28

American Chemical Society (ACS)

Journal of Medicinal Chemistry

scimago Q1

wos Q1

SJR: 1.801

CiteScore: 11.5

Impact factor: 6.8

ISSN: 00222623, 15204804

DOI: 10.1021/acs.jmedchem.6b01025

Copy DOI

PubMed ID: 27977197

Drug Discovery

Molecular Medicine

Abstract

Since its discovery 22 years ago, the bacterial cell-to-cell communication system, termed quorum sensing (QS), has shown potential as antipathogenic target. Previous studies reported that ajoene from garlic inhibits QS in opportunistic human pathogen Pseudomonas aeruginosa. In this study, screening of an in-house compound library revealed two sulfur-containing compounds which possess structural resemblance with ajoene and inhibit QS in bioreporter assay. Following a quantitative structure-activity relationship (SAR) study, 25 disulfide bond-containing analogues were synthesized and tested for QS inhibition activities. SAR study indicated that the allyl group could be replaced with other substituents, with the most active being benzothiazole derivative (IC50 = 0.56 μM). The compounds were able to reduce QS-regulated virulence factors (elastase, rhamnolipid, and pyocyanin) and successfully inhibit P. aeruginosa infection in murine model of implant-associated infection. Altogether, the QS inhibition activity of the synthesized compounds is encouraging for further exploration of novel analogues in antimicrobial drug development.

Found

2 citations

Duskaev Galimzhan

DSc in Agricultural sciences, associate professor, professor of the Russian Academy of Sciences

148 publications, 602 citations, 4 reviews

h-index: 15

Federal Research Centre of Biological Systems and Agrotechnologies of the Russian Academy of Sciences

1 citation

Krishna Suresh

🥼 🤝

PhD in Biological/biomedical sciences, senior lecturer, professor of the Zambia academy of sciences

85 publications, 1 327 citations, 87 reviews

h-index: 18

University of KwaZulu-Natal

Durban University of Technology

Research interests

Nanotechnology

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Cite this

GOST |

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GOST Copy

Fong J. et al. Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa // Journal of Medicinal Chemistry. 2016. Vol. 60. No. 1. pp. 215-227.

GOST all authors (up to 50) Copy

Fong J., Yuan M., Jakobsen T. H., Mortensen K. T., Delos Santos M. M. S., Chua S. L., Yang L., Tan C. H., Nielsen T. E., Givskov M. Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa // Journal of Medicinal Chemistry. 2016. Vol. 60. No. 1. pp. 215-227.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1021/acs.jmedchem.6b01025

UR - https://doi.org/10.1021/acs.jmedchem.6b01025

TI - Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa

T2 - Journal of Medicinal Chemistry

AU - Fong, July

AU - Yuan, Mingjun

AU - Jakobsen, Tim Holm

AU - Mortensen, Kim T

AU - Delos Santos, May Margarette Salido

AU - Chua, Song Lin

AU - Yang, Liang

AU - Tan, Choon Hong

AU - Nielsen, Thomas E

AU - Givskov, Michael

PY - 2016

DA - 2016/12/28

PB - American Chemical Society (ACS)

SP - 215-227

IS - 1

VL - 60

PMID - 27977197

SN - 0022-2623

SN - 1520-4804

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2016_Fong,

author = {July Fong and Mingjun Yuan and Tim Holm Jakobsen and Kim T Mortensen and May Margarette Salido Delos Santos and Song Lin Chua and Liang Yang and Choon Hong Tan and Thomas E Nielsen and Michael Givskov},

title = {Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa},

journal = {Journal of Medicinal Chemistry},

year = {2016},

volume = {60},

publisher = {American Chemical Society (ACS)},

month = {dec},

url = {https://doi.org/10.1021/acs.jmedchem.6b01025},

number = {1},

pages = {215--227},

doi = {10.1021/acs.jmedchem.6b01025}

}

MLA

Cite this

MLA Copy

Fong, July, et al. “Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa.” Journal of Medicinal Chemistry, vol. 60, no. 1, Dec. 2016, pp. 215-227. https://doi.org/10.1021/acs.jmedchem.6b01025.

Publisher

American Chemical Society (ACS)

Journal

Journal of Medicinal Chemistry

scimago Q1

wos Q1

SJR

1.801

CiteScore

11.5

Impact factor

6.8

ISSN

00222623 (Print)

15204804 (Electronic)