(Arene)Ru(II) complexes of epidermal growth factor receptor inhibiting tyrphostins with enhanced selectivity and cytotoxicity in cancer cells

被引：44

作者：

Biersack, B. ^{[1
]}

Zoldakova, M. ^{[1
]}

Effenberger, K. ^{[1
]}

Schobert, R. ^{[1
]}

机构：

[1] Univ Bayreuth, Organ Chem Lab, D-95440 Bayreuth, Germany

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 05期

关键词：

Ruthenium complexes; Tyrphostin; Anticancer drugs; Multi-drug resistance; EGFR inhibitor; TYROSINE KINASE INHIBITORS; ARENE COMPLEXES; IN-VITRO; DIFFERENTIATION; PROTEIN; DNA; RUTHENIUM(II); RESISTANCE; CARCINOMA; CISPLATIN;

D O I：

10.1016/j.ejmech.2010.01.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Ru(eta(6)-arene) complexes of epidermal growth factor receptor (EGFR) inhibiting tyrphostins 1a and 1b were prepared, characterized and tested for DNA interaction and bioactivity in four human tumor cell lines. The intrinsic cytotoxicity and cell line selectivity of o-hydroxyanisol la was greatly enhanced in its Ru(eta(6)-p-cymene) complex 2a and in its Ru(eta(6)-toluene) complex 3a. Complex 2a was particularly efficacious against multi-drug resistant EGFR(+) MCF-7/Topo breast carcinoma cells and also against mTOR-dependent EGER( -) HL-60 leukemia cells. Complex 3a showed enhanced activity only against 518A2 melanoma cells and HL-60 cells, which are both known to express the mTOR protein. DNA was strongly metallated (ca. 1.7-2%) by all new Ru complexes without undergoing topological changes. Apparently, by complexation to Ru fragments tyrphostin derivatives can address additional biological targets in a manner instrumental to antitumoral strategies. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：1972 / 1975

页数：4

共 27 条

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