Design of an amide N-glycoside derivative of β-glucogallin: a stable, potent, and specific inhibitor of aldose reductase

J Med Chem. 2014 Jan 9;57(1):71-7. doi: 10.1021/jm401311d. Epub 2013 Dec 23.

Abstract

β-Glucogallin (BGG), a major component of the Emblica officinalis medicinal plant, is a potent and selective inhibitor of aldose reductase (AKR1B1). New linkages (ether/triazole/amide) were introduced via high yielding, efficient syntheses to replace the labile ester, and an original two-step (90%) preparation of BGG was developed. Inhibition of AKR1B1was assessed in vitro and using transgenic lens organ cultures, which identified the amide linked glucoside (BGA) as a stable, potent, and selective therapeutic lead toward the treatment of diabetic eye disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Drug Design
  • Drug Stability
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Glycosides / chemical synthesis*
  • Glycosides / chemistry
  • Glycosides / pharmacology
  • Humans
  • Hydrolyzable Tannins / chemical synthesis
  • Hydrolyzable Tannins / chemistry*

Substances

  • Amides
  • Enzyme Inhibitors
  • Glycosides
  • Hydrolyzable Tannins
  • glucogallin
  • AKR1B1 protein, human
  • Aldehyde Reductase