Bioorganic & Medicinal Chemistry 2008-07-15

Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives.

Li Huang, Donglei Yu, Phong Ho, Keduo Qian, Kuo-Hsiung Lee, Chin-Ho Chen, Li Huang, Donglei Yu, Phong Ho, Keduo Qian, Kuo-Hsiung Lee, Chin-Ho Chen

Index: Bioorg. Med. Chem. 16 , 6696-6701, (2008)

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Abstract

This study discovered that glycyrrhetinic acid inhibited the human 20S proteasome at 22.3microM. 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 IC(50) of 0.22microM, which was approximately 100-fold more potent than glycyrrhetinic acid.