Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives.
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.
Department of Surgery, Box 2926, Duke University Medical Center, Durham, NC 27710-2926, USA.
Li
L
Huang
Donglei
D
Yu
Phong
P
Ho
Keduo
K
Qian
Kuo-Hsiung
KH
Lee
Chin-Ho
CH
Chen
D004951:Esterification; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D011480:Protease Inhibitors / Q000138:chemical synthesis; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship
D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D006034:Glycyrrhetinic Acid