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ID: ALA3400119

Journal: Bioorg Med Chem

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

Authors: Hansen MR, Jakobsen TH, Bang CG, Cohrt AE, Hansen CL, Clausen JW, Le Quement ST, Tolker-Nielsen T, Givskov M, Nielsen TE.

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.

CiteXplore: 25716005

DOI: 10.1016/j.bmc.2015.01.038