Hybrid angiogenesis inhibitors: synthesis and biological evaluation of bifunctional compounds based on 1-deoxynojirimycin and aryl-1,2,3-triazoles

Bioorg Med Chem Lett. 2008 Feb 1;18(3):954-8. doi: 10.1016/j.bmcl.2007.12.034. Epub 2007 Dec 23.

Abstract

Synthesis of hybrids of 1-deoxynojirimycin (DNJ) and 5-aryl-1,2,3-triazole as potential bifunctional inhibitors of angiogenesis is described. The DNJ component inhibits the biosynthesis of cell surface oligosaccharides necessary for angiogenesis, whereas the aryl-1,2,3-triazole inhibits methionine aminopeptidase II, a target in angiogenesis therapy. One bifunctional compound was a more potent inhibitor of angiogenesis in vitro than DNJ alone or the 5-aryl-1,2,3-triazole alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / chemical synthesis*
  • 1-Deoxynojirimycin / chemistry
  • 1-Deoxynojirimycin / pharmacology*
  • Aminopeptidases / antagonists & inhibitors*
  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Endothelial Cells / drug effects
  • Glycoside Hydrolase Inhibitors*
  • Humans
  • Metalloendopeptidases / antagonists & inhibitors*
  • Mice
  • Models, Molecular*
  • Molecular Structure
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Angiogenesis Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Triazoles
  • 1-Deoxynojirimycin
  • Aminopeptidases
  • methionine aminopeptidase 2
  • Metalloendopeptidases