Synthesis of Oleanolic Acid Dimers as Inhibitors of Glycogen Phosphorylase

被引：35

作者：

Cheng, Keguang ^{[1
,2
]}

Liu, Jun ^{[3
]}

Sun, Hongbin ^{[1
]}

Xie, Juan ^{[2
]}

机构：

[1] China Pharmaceut Univ, Ctr Drug Discovery, Coll Pharm, Nanjing 210009, Peoples R China

[2] UniverSud, CNRS, ENS Cachan, PPSM, F-94230 Cachan, France

[3] China Pharmaceut Univ, Jiangsu Ctr Drug Screening, Nanjing 210038, Peoples R China

来源：

CHEMISTRY & BIODIVERSITY | 2010年 / 7卷 / 03期

关键词：

PENTACYCLIC TRITERPENES; ALLOSTERIC SITE; DERIVATIVES; DISCOVERY; TARGET; DRUG;

D O I：

10.1002/cbdv.200900086

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 IC50 value (ca. 3 mu M) lower than that of oleanolic acid (IC50=14 mu M).

引用

页码：690 / 697

页数：8

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