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

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

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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

Keywords

  • Quorum sensing
  • Antibiotics
  • 1,2,3-Triazole
  • Homoserine lactone
  • Pseudomonas aeruginosa

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