Synthesis of 3-deoxypentacyclic triterpene derivatives as inhibitors of glycogen phosphorylase

Pu Zhang; Jia Hao; Jun Liu; Qian Lu; Huaming Sheng; Luyong Zhang; Hongbin Sun

doi:10.1021/np9002367

Synthesis of 3-deoxypentacyclic triterpene derivatives as inhibitors of glycogen phosphorylase

J Nat Prod. 2009 Aug;72(8):1414-8. doi: 10.1021/np9002367.

Authors

Pu Zhang¹, Jia Hao, Jun Liu, Qian Lu, Huaming Sheng, Luyong Zhang, Hongbin Sun

Affiliation

¹ Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, People's Republic of China.

PMID: 19642687
DOI: 10.1021/np9002367

Abstract

The 3-deoxy-2-keto derivatives 5 and 7 of oleanolic acid (1) and ursolic acid (2), respectively, served as precursors to the synthesis of 35 3-deoxy derivatives of pentacyclic triterpenes. The synthesized compounds were biologically assayed for their inhibitory activity against rabbit muscle glycogen phosphorylase a (GPa). Among this series of compounds, 2alpha-hydroxyurs-12-en-28-oic acid (18) (IC(50) = 1.2 microM) exhibited the most potent activity. Preliminary structure-activity relationship analysis for the 3-deoxy triterpene derivatives as GP inhibitors is also discussed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Drug Design
Glycogen Phosphorylase / antagonists & inhibitors*
Molecular Structure
Muscle, Skeletal / drug effects
Muscle, Skeletal / enzymology
Oleanolic Acid / chemical synthesis
Oleanolic Acid / chemistry
Oleanolic Acid / pharmacology
Pentacyclic Triterpenes / chemical synthesis*
Pentacyclic Triterpenes / chemistry
Pentacyclic Triterpenes / pharmacology*
Rabbits
Structure-Activity Relationship
Triterpenes / chemical synthesis
Triterpenes / chemistry
Triterpenes / pharmacology
Ursolic Acid

Substances

Pentacyclic Triterpenes
Triterpenes
Oleanolic Acid
corosolic acid
Glycogen Phosphorylase