Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa
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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.
Originalsprog | Engelsk |
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Tidsskrift | Bioorganic & Medicinal Chemistry |
Vol/bind | 23 |
Udgave nummer | 7 |
Sider (fra-til) | 1638-1650 |
Antal sider | 13 |
ISSN | 0968-0896 |
DOI | |
Status | Udgivet - 2015 |
ID: 135482604