Synthesis and Biological Evaluation of Asiatic Acid Derivatives as Inhibitors of Glycogen Phosphorylases

Abstract magnified image 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 μ M ) exhibited more potent activity than its parent compound 1 ( IC 50 =17 μ M ). SAR Analysis showed that asiatic acid ( 1 ) possessing a 2 α ‐OH function exhibited more potent GP inhibitory activity than eriantic acid B ( 27 ) which possesses a 2 β ‐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.