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; IC50 = 3.8 mu m) exhibited more potent activity than its parent compound I (IC50 = 17 mu m). SAR Analysis showed that asiatic acid (1) possessing a 2 alpha-OH function exhibited more potent GP inhibitory activity than eriantic acid B (27) which possesses it 2 beta-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.