title: Second generation of thiazolylmannosides, FimH antagonists for E. coli-induced Crohn's disease.
abstract: The anti-adhesive strategy, consisting of disrupting bacterial attachment to the host cells, is widely explored as an alternative to antibiotic therapies. Recently, thiazolylmannosides (TazMans) have been identified as strong anti-adhesives of E. coli strains implied in the gut inflammation of patients with Crohn's disease. In this work, we developed a second generation of TazMans with improved chemical stability. The anomeric nitrogen was substituted by short linkers and the compounds were assessed against the bacterial adhesin FimH and the clinically isolated LF82 E. coli strain in four in vitro assays. The results obtained on the FimH adhesin alone and the whole bacteria enabled the identification of a candidate for further in vivo evaluations.
authors.affiliation: LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France. sebastien.gouin@univ-nantes.fr.
authors.forename: T
authors.initials: T
authors.lastname: Chalopin
authors.forename: D
authors.initials: D
authors.lastname: Alvarez Dorta
authors.forename: A
authors.initials: A
authors.lastname: Sivignon
authors.forename: M
authors.initials: M
authors.lastname: Caudan
authors.forename: T I
authors.initials: TI
authors.lastname: Dumych
authors.forename: R O
authors.initials: RO
authors.lastname: Bilyy
authors.forename: D
authors.initials: D
authors.lastname: Deniaud
authors.forename: N
authors.initials: N
authors.lastname: Barnich
authors.forename: J
authors.initials: J
authors.lastname: Bouckaert
authors.forename: S G
authors.initials: SG
authors.lastname: Gouin
mesh_terms: D018830:Adhesins, Escherichia coli; D003424:Crohn Disease / Q000188:drug therapy* / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000187:drug effects* / Q000472:pathogenicity; D036781:Fimbriae Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008362:Mannosides / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018830:Adhesins, Escherichia coli; D008362:Mannosides; D013844:Thiazoles; C058769:fimH protein, E coli; D036781:Fimbriae Proteins