Ruthenium polypyridyl complexes and their modes of interaction with DNA: Is there a correlation between these interactions and the antitumor activity of the compounds?
Open Access
- 16 December 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in JBIC Journal of Biological Inorganic Chemistry
- Vol. 14 (3), 439-448
- https://doi.org/10.1007/s00775-008-0460-x
Abstract
Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L1L2](2−n)+, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{μ-H2N(CH2)6NH2}]4+. The ligand tpy is 2,2′:6′,2″-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,2′-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl−, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.Keywords
This publication has 70 references indexed in Scilit:
- Dinuclear Ruthenium(II) Triple‐Stranded Helicates: Luminescent Supramolecular Cylinders That Bind and Coil DNA and Exhibit Activity against Cancer Cell LinesAngewandte Chemie-International Edition, 2007
- Structure-dependent in vitro cytotoxicity of the isomeric complexes [Ru(L)2Cl2] (L=o-tolylazopyridine and 4-methyl-2-phenylazopyridine) in comparison to [Ru(azpy)2Cl2]JBIC Journal of Biological Inorganic Chemistry, 2004
- Intramolecular DNA Coiling Mediated by a Metallo-Supramolecular CylinderAngewandte Chemie-International Edition, 2001
- Effects of ruthenium complexes on experimental tumors: irrelevance of cytotoxicity for metastasis inhibitionChemico-Biological Interactions, 1995
- Anti-leukaemic action of RuCl2(DMSO)4 isomers and prevention of brain involvement on P388 leukaemia and on P388DDP sublineEuropean Journal Of Cancer, 1993
- Comparison of the sulforhodamine B protein and tetrazolium (MTT) assays for in vitro chemosensitivity testingEuropean Journal of Cancer and Clinical Oncology, 1991
- Oxidation of isopropylamine and related amines coordinated to ruthenium. Formation of monodentate imine and alkylideneamido complexes of rutheniumInorganic Chemistry, 1984
- Rearrangement of a platinum (II) complex in DNA from intercalation outer-sphere position to non-intercalation coordinationFEBS Letters, 1978
- A Further Examination of the Molecular Weight and Size of Desoxypentose Nucleic AcidJournal of the American Chemical Society, 1954
- Über einige Derivate und Oxydationsprodukte von 2‐Amino‐pyridinBerichte der deutschen chemischen Gesellschaft (A and B Series), 1927