title: Tuning the hydrophobicity of ruthenium(II)-arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy.
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.
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
authors.forename: Claudine
authors.initials: C
authors.lastname: Scolaro
authors.forename: Adrian B
authors.initials: AB
authors.lastname: Chaplin
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
authors.forename: Alberta
authors.initials: A
authors.lastname: Bergamo
authors.forename: Moreno
authors.initials: M
authors.lastname: Cocchietto
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Gianni
authors.initials: G
authors.lastname: Sava
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
mesh_terms: D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017975:Ruthenium Compounds / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D017975:Ruthenium Compounds