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Scolaro C, Chaplin AB, Hartinger CG, Bergamo A, Cocchietto M, Keppler BK, Sava G, Dyson PJ: Tuning the hydrophobicity of ruthenium (II)-arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy. Dalton Trans. 2007 Nov 21;(43):5065-72. Epub 2007 Sep 26.
The antitumour activity of the organometallic ruthenium (ii)-arene mixed phosphine complexes, [Ru (eta (6)-p-cymene) Cl (PTA)(PPh (3))] BF (4) and [Ru (eta (6)-C (6) H (5) CH (2) CH (2) OH) Cl (PTA)(PPh (3))] BF (4) (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)] and [Ru (eta (6)-C (6) H (5) CH (2) CH (2) OH) Cl (2)(PTA)] . The results show that the addition of the PPh (3) ligand to 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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