title: Fusaric acid and analogues as Gram-negative bacterial quorum sensing inhibitors.
abstract: Taking advantage of microwave-assisted synthesis, efficient and expedite procedures for preparation of a library of fusaric acid and 39 analogues are reported. The fusaric acid analogues were tested in cell-based screening assays for inhibition of the las and rhl quorum sensing system in Pseudomonas aeruginosa and the lux quorum sensing system in Vibrio fischeri. Eight of the 40 compounds in the library including fusaric acid inhibited lux quorum sensing and one compound inhibited activity of the las quorum sensing system. To our delight, none of the compounds showed growth inhibitory effects in the tested concentration ranges.
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
authors.forename: Truong Thanh
authors.initials: TT
authors.lastname: Tung
authors.affiliation: Costerton Biofilm Center, Faculty of Health Sciences, Department of Immunology and Microbiology, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Tim Holm
authors.initials: TH
authors.lastname: Jakobsen
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark; Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Trong Tuan
authors.initials: TT
authors.lastname: Dao
authors.affiliation: Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Anja Thoe
authors.initials: AT
authors.lastname: Fuglsang
authors.affiliation: Costerton Biofilm Center, Faculty of Health Sciences, Department of Immunology and Microbiology, Blegdamsvej 3B, 2200 Copenhagen, Denmark; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 637551, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Givskov
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark. Electronic address: soren.christensen@sund.ku.dk.
authors.forename: Søren Brøgger
authors.initials: SB
authors.lastname: Christensen
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark. Electronic address: john.nielsen@sund.ku.dk.
authors.forename: John
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D015195:Drug Design; D005669:Fusaric Acid / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D011550:Pseudomonas aeruginosa / Q000166:cytology* / Q000187:drug effects*; D053038:Quorum Sensing / Q000187:drug effects*
chemical_list: D006180:Proton-Translocating ATPases; D005669:Fusaric Acid
keywords: Fusaric acid; Microwave-assisted synthesis; Quorum sensing inhibitors