Tuning the hydrophobicity of ruthenium(ii)–arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy
- 26 September 2007
- journal article
- Published by Royal Society of Chemistry (RSC) in Dalton Transactions
- No. 43,p. 5065-5072
- https://doi.org/10.1039/b705449a
Abstract
The antitumour activity of the organometallic ruthenium(II)–arene mixed phosphine complexes, [Ru(η6-p-cymene)Cl(PTA)(PPh3)]BF41b and [Ru(η6-C6H5CH2CH2OH)Cl(PTA)(PPh3)]BF42b (PTA = 1,3,5-triaza-7-phosphaadamantane), have been evaluated in vitro and compared to their RAPTA analogues, [Ru(η6-p-cymene)Cl2(PTA)] 1a and [Ru(η6-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.Keywords
This publication has 55 references indexed in Scilit:
- ESI–MS Characterisation of Protein Adducts of Anticancer Ruthenium(II)‐Arene PTA (RAPTA) ComplexesChemMedChem, 2007
- Synthesis, Characterization, and DNA Binding of New Water-Soluble Cyclopentadienyl Ruthenium(II) Complexes Incorporating PhosphinesInorganic Chemistry, 2006
- KP1019 (FFC14A) from bench to bedside: preclinical and early clinical development ? an overviewInternational journal of clinical pharmacology and therapeutics, 2005
- Actin-dependent tumour cell adhesion after short-term exposure to the antimetastasis ruthenium complex NAMI-AEuropean Journal of Cancer, 2004
- Biologically Active Platinum Complexes Containing 8-Thiotheophylline and 8-(Methylthio)theophyllineInorganic Chemistry, 2004
- 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)Electronic supplementary information (ESI) available: synthesis, 31P{1H}, 1H, 13C NMR characterisation and elemental analysis of 1 and 2. See http://www.rsc.org/suppdata/cc/b2/b210102e/Chemical Communications, 2002
- Interactions of cisplatin and transplatin with proteins: Comparison of binding kinetics, binding sites and reactivity of the Pt-protein adducts of cisplatin and transplatin towards biological nucleophilesJournal of Inorganic Biochemistry, 2002
- Preferential binding of cisplatin to mitochondrial DNA of Chinese hamster ovary cellsMutation Research Letters, 1995
- High-resolution three-dimensional structure of horse heart cytochrome cJournal of Molecular Biology, 1990
- Structure of ubiquitin refined at 1.8ÅresolutionJournal of Molecular Biology, 1987