Abstract Title:

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

Abstract Source:

J Med Chem. 2017 Jan 12 ;60(1):215-227. Epub 2016 Dec 28. PMID: 27977197

Abstract Author(s):

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

Article Affiliation:

July Fong


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 (IC= 0.56μM). 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.

Study Type : In Vitro Study

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