Mannosylated N-aryl substituted 3-hydroxypyridine-4-ones: synthesis, hemagglutination inhibitory properties, and molecular modeling

Chem Biol Drug Des. 2014 Oct;84(4):393-401. doi: 10.1111/cbdd.12329. Epub 2014 Jun 3.

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.

Keywords: Escherichia coli; FimH lectin; N-aryl-substituted 3-hydroxypyridine-4-ones; hemagglutination; molecular modeling; α-mannopyranosides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Escherichia coli / metabolism
  • Binding Sites
  • Escherichia coli / metabolism
  • Fimbriae Proteins / antagonists & inhibitors
  • Fimbriae Proteins / metabolism
  • Hemagglutination / drug effects
  • Mannosides / chemistry*
  • Molecular Docking Simulation
  • Platelet Aggregation Inhibitors / pharmacology
  • Protein Structure, Tertiary
  • Pyridones / chemical synthesis
  • Pyridones / chemistry*
  • Pyridones / pharmacology
  • Quantum Theory

Substances

  • Adhesins, Escherichia coli
  • Mannosides
  • Platelet Aggregation Inhibitors
  • Pyridones
  • fimH protein, E coli
  • 3-hydroxy-4-pyridone
  • Fimbriae Proteins