Discovery of a Highly Tumor-Selective Organometallic Ruthenium(II)-Arene Complex

被引：57

作者：

Clavel, Catherine M. ^{[1
]}

Paunescu, Emilia ^{[1
]}

Nowak-Sliwinska, Patrycja ^{[1
]}

Griffioen, Arjan W. ^{[2
]}

Scopelliti, Rosario ^{[1
]}

Dyson, Paul J. ^{[1
]}

机构：

[1] Ecole Polytech Fed Lausanne, Inst Sci & Ingn Chim, CH-1015 Lausanne, Switzerland

[2] VUMC Canc Ctr Amsterdam, Angiogenesis Lab, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 08期

基金：

瑞士国家科学基金会;

关键词：

ARENE ANTICANCER COMPLEXES; IN-VITRO; RUTHENIUM COMPLEXES; PHASE-I; BINDING; CANCER; DESIGN; DRUGS; INHIBITORS; REACTIVITY;

D O I：

10.1021/jm5002748

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A ruthenium(II)-arene complex with a perfluoroalkyl-ligand was found to display remarkable selectivity toward cancer cells. IC50 values on several cancer cell lines are in the range of 25-45 mu M, and no cytotoxic effect was observed on nontumorigenic (HEK-293) cells at concentrations up to 500 mu M (the maximum concentration tested). Consequently, this complex was used as the basis for the development of a number of related derivatives, which were screened in cancerous and noncancerous cell lines. The lead compound was then evaluated in vivo for antiangiogenic activity in the CAM model and in a xenografted ovarian carcinoma tumor (A2780) grown on the CAM. A 90% reduction in the tumor growth was observed.

引用

页码：3546 / 3558

页数：13

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