Synthesis and biological evaluation of asiatic acid derivatives as inhibitors of glycogen phosphorylases.
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.
Zhang
Liying
L
Center for Drug Discovery, School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, P. R. China.
Chen
Jun
J
Gong
Yanchun
Y
Liu
Jun
J
Zhang
Luyong
L
Hua
Weiyi
W
Sun
Hongbin
H
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053978:Pentacyclic Triterpenes; D011817:Rabbits; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C017032:asiatic acid; D024981:Glycogen Phosphorylase