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.