TY - JOUR
T1 - Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa
AU - Hansen, Mette Reimert
AU - Jakobsen, Tim Holm
AU - Bang, Claus Gunnar
AU - Cohrt, Anders Emil
AU - Hansen, Casper Lykke
AU - Clausen, Janie Regitse Waël
AU - Le Quement, Sebastian Thordal
AU - Tolker-Nielsen, Tim
AU - Givskov, Michael
AU - Nielsen, Thomas
N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.bmc.2015.01.038
DO - 10.1016/j.bmc.2015.01.038
M3 - Journal article
C2 - 25716005
SN - 0968-0896
VL - 23
SP - 1638
EP - 1650
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
IS - 7
ER -