期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 52, 期 -, 页码 242-250出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2012.03.024
关键词
Spirolactone-type diterpenoid; Enmein-type diterpenoid; ent-6,7-seco-Oridonin derivatives; Cytotoxicity; Anti-tumor activity; Structure-activity relationship
资金
- National Natural Science Fund [30973610]
- Specialized Research Fund for the Doctoral Program of Higher Education [20100096110001]
- Project for Research and Innovation of Graduates in Universities of Jiangsu Province [800]
- Fundamental Research Funds for the Central Universities [JKY2011030]
- Ministry of Education of China [108069]
Starting from commercial available natural product oridonin (1), a practical synthesis of ent-6,7-seco-oridonin derivatives (2, 3, 5, and 9) was accomplished and their biological activities were evaluated. The conversion of spirolactone-type diterpenoid to enmein-type was first completed. The results demonstrated that all synthesized ent-6,7-seco-oridonin derivatives could markedly inhibit the proliferation of cancer cells. Compared with Taxol, the most cytotoxic compound 5 has similar potency in A549 cell and slightly less cytotoxicity in Bel-7402 cell. Compound 5 was also more potent than parent compound oridonin in mice with MGC-803 gastric cancer in vivo. Then a series of novel 14-O-derivatives of 5 were further designed and synthesized, which showed better activity than 5 and similar activity as Taxol in vitro. The structure activity relationships of oridonin derivatives were also discussed in the present investigations. (C) 2012 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据