Synthesis and evaluation of iminocoumaryl and coumaryl derivatized glycosides as galectin antagonists

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3516-20. doi: 10.1016/j.bmcl.2014.05.063. Epub 2014 Jun 9.

Abstract

A collection of iminocoumarylmethyl glycoside derivatives have been prepared by copper-catalyzed multi-component reaction of carbohydrate propargyl derivatives, sulfonyl azides, and salicylaldehyde or o-hydroxy acetophenone. The method is simple, versatile to all three components, and exceptionally high yielding. The carbohydrate N-sulfonyl iminocoumarine hybrid molecules were evaluated for binding galectin-1, -2, -3, -4N, -4C, -7, -8N, -9N, and 9C using a competitive fluorescence polarization assay. Selective compounds were identified against galectin-3, 7, 8N, and 9N with up to 40-fold affinity enhancements relative to methyl α-d-galactopyranoside due to the coumarylmethyl moieties.

Keywords: Antagonist; Coumarine; Galectin; Iminocoumarine; Multicomponent reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coumaric Acids / chemistry*
  • Dose-Response Relationship, Drug
  • Galectins / antagonists & inhibitors*
  • Glycosides / chemical synthesis
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Coumaric Acids
  • Galectins
  • Glycosides