Synthesis and cytotoxicity studies of new dimethylamino-functionalised and aryl-substituted titanocene anti-cancer agents

被引：25

作者：

Pampillon, Clara ^{[1
]}

Claffey, James ^{[1
]}

Strohfeldt, Katja ^{[1
]}

Tacke, Matthias ^{[1
]}

机构：

[1] Univ Coll Dublin, Ctr Synthesis & Chem Biol, Sch Chem & Chem Biol, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 43卷 / 01期

基金：

爱尔兰科学基金会;

关键词：

anti-cancer agents; cis-platin; titanocene; fulvene; dimethylamino-functionalised metallocenes; LLC-PK;

D O I：

10.1016/j.ejmech.2007.02.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated aryl species [p-N,N-dimethylanilinyl lithium, p-anisyl lithium and 4-lithio-benzo[1.3]dioxole (2a-c)], the corresponding lithium cyclopentadienide intermediates 4a-c were formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised and aryl-substituted titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 54, 45 and 26 mu M for titanocenes 5a, b and c, respectively. The most cytotoxic titanocene in this paper, 5c is approximately 10 times less cytotoxic than cis-platin, which showed an IC50 value of 3.3 mu M, when tested on the LLC-PK cell line, but approximately 100 times better than titanocene dichloride. (C) 2007 Elsevier Masson SAS. All rights reserved.

引用

页码：122 / 128

页数：7

共 41 条

[1]

[Anonymous], 2004, GAUSS 03 REV C 02

[2] Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer [J].