Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives Original Research Article

This study discovered that glycyrrhetinic acid inhibited the human 20S proteasome at 22.3 μM. Esterification of the C-3 hydroxyl group on glycyrrhetinic acid with various carboxylic acid reagents yielded a series of analogs with marked improved potency. Among the derivatives, glycyrrhetinic acid 3-O-isophthalate (17) was the most potent compound with IC50 of 0.22 μM, which was approximately 100-fold more potent than glycyrrhetinic acid.