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Dalton Transactions

The international journal for inorganic, organometallic and bioinorganic chemistry



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Dalton Trans., 2007, 5065 - 5072, DOI: 10.1039/b705449a

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

Claudine Scolaro, Adrian B. Chaplin, Christian G. Hartinger, Alberta Bergamo, Moreno Cocchietto, Bernhard K. Keppler, Gianni Sava and Paul J. Dyson

The antitumour activity of the organometallic ruthenium(II)–arene mixed phosphine complexes, [Ru(6-p-cymene)Cl(PTA)(PPh3)]BF4 1b and [Ru(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(6-p-cymene)Cl2(PTA)] 1a and [Ru(6-C6H5CH2CH2OH)Cl2(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.

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