title: Mannosylated N-aryl substituted 3-hydroxypyridine-4-ones: synthesis, hemagglutination inhibitory properties, and molecular modeling.
abstract: Structural alterations of the aglycon portions of α-mannosides influence their inhibitory potency toward type 1-fimbriated Escherichia coli. The aim of our work was to prepare and explore inhibitory properties of novel mannosylated N-aryl-substituted 3-hydroxypyridine-4-ones because they possess needed structural characteristics as possible FimH antagonists. Hemagglutination inhibitory tests showed that the examined 3-hydroxypyridine-4-one α-mannosides exhibited better inhibitory activity than methyl α-d-mannopyranoside used as a reference compound. Molecular modeling studies revealed the specific interactions responsible for the observed binding activities toward the mannose-specific FimH lectin. The activity depends on the substituent in p-position on the aglycon aromatic ring.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000, Zagreb, Croatia.
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Car
authors.forename: Tomica
authors.initials: T
authors.lastname: Hrenar
authors.forename: Vesna
authors.initials: V
authors.lastname: Petrović Peroković
authors.forename: Rosana
authors.initials: R
authors.lastname: Ribić
authors.forename: Mateja
authors.initials: M
authors.lastname: Seničar
authors.forename: Srđanka
authors.initials: S
authors.lastname: Tomić
mesh_terms: D018830:Adhesins, Escherichia coli / Q000378:metabolism; D001665:Binding Sites; D004926:Escherichia coli / Q000378:metabolism; D036781:Fimbriae Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006384:Hemagglutination / Q000187:drug effects; D008362:Mannosides / Q000737:chemistry*; D062105:Molecular Docking Simulation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011789:Quantum Theory
chemical_list: D018830:Adhesins, Escherichia coli; D008362:Mannosides; D010975:Platelet Aggregation Inhibitors; D011728:Pyridones; C058769:fimH protein, E coli; C020366:3-hydroxy-4-pyridone; D036781:Fimbriae Proteins
keywords: Escherichia coli; FimH lectin; N-aryl-substituted 3-hydroxypyridine-4-ones; hemagglutination; molecular modeling; α-mannopyranosides