Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa

Research output: Contribution to journalJournal articleResearchpeer-review

Mette Reimert Hansen, Tim Holm Jakobsen, Claus Gunnar Bang, Anders Emil Cohrt, Casper Lykke Hansen, Janie Regitse Waël Clausen, Sebastian Thordal Le Quement, Tim Tolker-Nielsen, Michael Givskov, Thomas Nielsen

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.

Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Volume23
Issue number7
Pages (from-to)1638-1650
Number of pages13
ISSN0968-0896
DOIs
Publication statusPublished - 2015

ID: 135482604