Synthesis and biological evaluation of asiatic acid derivatives as inhibitors of glycogen phosphorylases.

Abstract

Twenty-four asiatic acid derivatives have been synthesized and biologically evaluated as inhibitors of glycogen phosphorylase (GP). Within this series of compounds, asiatic acid benzyl ester (23; IC(50)=3.8 microM) exhibited more potent activity than its parent compound 1 (IC(50)=17 microM). SAR Analysis showed that asiatic acid (1) possessing a 2alpha-OH function exhibited more potent GP inhibitory activity than eriantic acid B (27) which possesses a 2beta-OH function. Further lead optimization based on 1 is needed to find more effective asiatic acid derivatives as antidiabetic agents with protective effects against ischemic diabetic complications.

• Authors: Liying Zhang, Jun Chen, Yanchun Gong, Jun Liu, Luyong Zhang, Weiyi Hua, Hongbin Sun
• Journal: Chemistry & biodiversity (Chem Biodivers) Vol. 6 Issue 6 Pg. 864-74 (Jun 2009) ISSN: 1612-1880 [Electronic] Switzerland
• PMID: 19551727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Hypoglycemic Agents
• Pentacyclic Triterpenes
• Triterpenes
• asiatic acid
• Glycogen Phosphorylase

Topics

• Animals
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• Glycogen Phosphorylase (antagonists & inhibitors, metabolism)
• Hypoglycemic Agents (chemical synthesis, chemistry, pharmacology)
• Pentacyclic Triterpenes
• Rabbits
• Structure-Activity Relationship
• Triterpenes (chemical synthesis, chemistry, pharmacology)