Synthesis and biological evaluations of new analogs of 2-methoxyestradiol: Inhibitors of tubulin and angiogenesis

被引：27

作者：

Solum, Eirik Johansson ^{[1
]}

Cheng, Jing-Jy ^{[2
,3
]}

Sorvik, Irene B. ^{[4
]}

Paulsen, Ragnhild E. ^{[4
]}

Vik, Anders ^{[1
]}

Hansen, Trond Vidar ^{[1
]}

机构：

[1] Univ Oslo, Sch Pharm, Dept Pharmaceut Chem, N-0316 Oslo, Norway

[2] Natl Res Inst Chinese Med, Taipei, Taiwan

[3] Natl Yang Ming Univ, Inst Biophoton, Taipei 112, Taiwan

[4] Univ Oslo, Sch Pharm, Dept Pharmaceut Biosci, N-0316 Oslo, Norway

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 85卷

关键词：

2-Methoxyestradiol; Anti-cancer; Tubulin inhibition; Anti-angiogenesis; Steroids; ORAL; 2-METHOXYESTRADIOL; 1,2,3-TRIAZOLE ANALOGS; STEROIDAL ALKALOIDS; COMBRETASTATIN A-4; CORTISTATIN; MECHANISMS; AGENT; METABOLITE; REDUCTION; APOPTOSIS;

D O I：

10.1016/j.ejmech.2014.08.002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis, cytotoxicity, inhibition of tubulin polymerization and anti-angiogenic effects of 15 analogs of 2-methoxyestradiol (1) are reported. The biological studies revealed that the position of nitrogen atom in the heterocyclic ring is important for inhibition of both tubulin polymerization and angiogenesis. The most potent inhibitors were compounds 11f and 13e, with a 6-substituted isoquinoline ring in the 17-position of the steroid skeleton. Moreover, low estrogen activity was observed for the analogs tested at 10 mu M concentrations. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：391 / 398

页数：8

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