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Title: Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa
Authors: Fong, July
Yuan, Mingjun
Jakobsen, Tim Holm
Mortensen, Kim T.
Delos Santos, May Margarette Salido
Chua, Song Lin
Yang, Liang
Tan, Choon Hong
Givskov, Michael
Nielsen, Thomas Eiland
Keywords: Disulfide Bond
Ajoene Analogues
Issue Date: 2016
Source: Fong, J., Yuan, M., Jakobsen, T. H., Mortensen, K. T., Delos Santos, M. M. S., Chua, S. L., et al. (2017). Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa. Journal of Medicinal Chemistry, 60(1), 215-227.
Series/Report no.: Journal of Medicinal Chemistry
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.
ISSN: 0022-2623
DOI: 10.1021/acs.jmedchem.6b01025
Rights: © 2016 American Chemical Society.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles
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