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Synthesis of Oleanolic Acid Dimers as Inhibitors of Glycogen Phosphorylase
Author(s) -
Cheng Keguang,
Liu Jun,
Sun Hongbin,
Xie Juan
Publication year - 2010
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200900086
Subject(s) - glycogen phosphorylase , oleanolic acid , chemistry , dimer , glycogen , biochemistry , click chemistry , stereochemistry , phosphorylase kinase , amide , enzyme , combinatorial chemistry , organic chemistry , medicine , alternative medicine , pathology
Recently, oleanolic acid was found to be an inhibitor of glycogen phosphorylase. For further structural modification, we have synthesized several dimers of oleanolic acid by using amide, ester, or triazole linkage with click chemistry. The click chemistry was shown to be the most efficient method for the dimer synthesis. Nearly quantitative yield of triazole‐linked dimers was obtained. Biological evaluation of the synthesized dimers as inhibitors of glycogen phosphorylase has been described. Four of six dimers exhibited inhibitory activity against rabbit muscle glycogen phosphorylase a (RMGPa), with compounds 2 and 7 as the most potent inhibitors, which displayed an IC 50 value ( ca. 3 μ M ) lower than that of oleanolic acid ( IC 50 =14 μ M ).