Synthesis and evaluation of a novel series of heterocyclic oleanolic acid derivatives with anti-osteoclast formation activity

被引：58

作者：

Li, Jun-Feng ^{[1
]}

Zhao, Yu ^{[1
]}

Cai, Min-Min ^{[1
]}

Li, Xiao-Fei ^{[1
]}

Li, Jian-Xin ^{[1
]}

机构：

[1] Nanjing Univ, Sch Chem & Chem Engn, Key Lab Analyt Chem Life Sci, Nanjing 210093, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 07期

关键词：

Oleanolic acid; Heterocyclic derivatives; Osteoclast formation; Inhibitory activity; SAR; KETOAMIDE-BASED INHIBITORS; CYSTEINE PROTEASE; URSOLIC ACID; POTENT; BISPHOSPHONATES;

D O I：

10.1016/j.ejmech.2008.12.024

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Oleanolic acid with anti-bone resorption effect was an active component discovered in a medicinal plant of Achyranthes bidentata. A series of heterocyclic derivatives of oleanolic acid including indole, pyrazine, quinoxaline, quinoline moieties and their natural amino acid amides were synthesized. Their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) and cytotoxicity of the selected derivatives were evaluated. Among the derivatives, compounds 2a and 8a displayed quite a potent activity even at 200 nM. The structure-activity relationships of the derivatives were also discussed. (C) 2008 Elsevier Masson SAS. All rights reserved.

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页码：2796 / 2806

页数：11

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