Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives

Bioorg Med Chem. 2008 Jul 15;16(14):6696-701. doi: 10.1016/j.bmc.2008.05.078. Epub 2008 Jun 5.

Abstract

This study discovered that glycyrrhetinic acid inhibited the human 20S proteasome at 22.3microM. Esterification of the C-3 hydroxyl group on glycyrrhetinic acid with various carboxylic acid reagents yielded a series of analogs with marked improved potency. Among the derivatives, glycyrrhetinic acid 3-O-isophthalate (17) was the most potent compound with IC(50) of 0.22microM, which was approximately 100-fold more potent than glycyrrhetinic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Esterification
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / chemical synthesis
  • Glycyrrhetinic Acid / pharmacology
  • Humans
  • Protease Inhibitors / chemical synthesis
  • Proteasome Inhibitors*
  • Structure-Activity Relationship

Substances

  • Protease Inhibitors
  • Proteasome Inhibitors
  • Glycyrrhetinic Acid