Journal article
Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa
In an attempt to devise new antimicrobial treatments for biofilm infections, the bacterial cell-cell communication system termed quorum sensing has emerged as an attractive target. It has proven possible to intercept the communication system by synthetic non-native ligands and thereby lower the pathogenesis and antibiotic tolerance of a bacterial biofilm.
To identify the structural elements important for antagonistic or agonistic activity against the Pseudomonas aeruginosa LasR protein, we report the synthesis and screening of new triazole-containing mimics of natural N-acyl homoserine lactones. A series of azide- and alkyne-containing homoserine lactone building blocks was used to prepare an expanded set of 123 homoserine lactone analogues through a combination of solution- and solid-phase synthesis methods.
The resulting compounds were subjected to cell-based quorum sensing screening assays, thereby revealing several bioactive compounds, including 13 compounds with antagonistic activity and 9 compounds with agonistic activity. (C) 2015 Elsevier Ltd. All rights reserved.
Language: | English |
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Year: | 2015 |
Pages: | 1638-1650 |
ISSN: | 14643391 and 09680896 |
Types: | Journal article |
DOI: | 10.1016/j.bmc.2015.01.038 |
ORCIDs: | 0000-0002-9751-474X , 0000-0002-1671-2155 and 0000-0001-5004-8609 |