Tuning the hydrophobicity of ruthenium(II)-arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy

被引：137

作者：

Scolaro, Claudine

Chaplin, Adrian B.

Hartinger, Christian G.

Bergamo, Alberta

Cocchietto, Moreno

Keppler, Bernhard K.

Sava, Gianni

Dyson, Paul J. ^{[1
]}

机构：

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

[2] Callerio Fdn Onlus, I-34127 Trieste, Italy

[3] Univ Trieste, Dipartimento Sci Biomed, I-34127 Trieste, Italy

[4] Univ Vienna, Inst Inorgan Chem, A-1090 Vienna, Austria

来源：

DALTON TRANSACTIONS | 2007年 / 43期

关键词：

D O I：

10.1039/b705449a

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

The antitumour activity of the organometallic ruthenium( II)-arene mixed phosphine complexes, [Ru(eta(6)-p-cymene)Cl( PTA)( PPh3)]BF4 1b and [Ru(eta(6)-C6H5CH2CH2OH)Cl(PTA)(PPh3)]BF4 2b (PTA = 1,3,5-triaza-7-phosphaadamantane), have been evaluated in vitro and compared to their RAPTA analogues, [Ru(eta(6)-p-cymene)Cl-2(PTA)] 1a and [Ru(eta(6)-C6H5CH2CH2OH)Cl-2(PTA)] 2a. The results show that the addition of the PPh3 ligand to 2a increases the cytotoxicity towards the TS/A adenocarcinoma cancer cells, which correlates with increased uptake, but also increases cytotoxicity to non-tumourigenic HBL-100 cells, thus decreasing selectivity. The decrease in selectivity has been correlated to increased DNA interactions relative to proteins, demonstrated by reactivity of the compounds with a 14-mer oligonucleotide and the model proteins ubiquitin and cytochrome-c.

引用

页码：5065 / 5072

页数：8

共 63 条

[1] Synthesis, catalytic properties and biological activity of new water soluble ruthenium cyclopentadienyl PTA complexes [(C5R5)RuCl(PTA)2] (R = H, Me; PTA=1,3,5-triaza-7-phosphaadamantane) [J].