1. Tuning the hydrophobicity of ruthenium(ii)-arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy
- Author
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Christian G. Hartinger, Gianni Sava, Adrian B. Chaplin, Paul J. Dyson, Moreno Cocchietto, Claudine Scolaro, Bernhard K. Keppler, Alberta Bergamo, Scolaro, C, Chaplin, Ab, Hartinger, Cg, Bergamo, A, Cocchietto, M, Keppler, Bk, Sava, Gianni, and Dyson, Pj
- Subjects
Models, Molecular ,Spectrometry, Mass, Electrospray Ionization ,Magnetic Resonance Spectroscopy ,Oligonucleotide ,Chemistry ,Stereochemistry ,Ligand ,chemistry.chemical_element ,Hydrogen Bonding ,In vitro ,Ruthenium ,Inorganic Chemistry ,chemistry.chemical_compound ,otorhinolaryngologic diseases ,Ruthenium Compounds ,Reactivity (chemistry) ,Selectivity ,Cytotoxicity ,Phosphine - Abstract
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.
- Published
- 2007