Ruthenium polypyridyl complexes and their modes of interaction with DNA: Is there a correlation between these interactions and the antitumor activity of the compounds?

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00775-008-0460-x) contains supplementary material, which is available to authorized users.

Mechanism of Cytotoxicity and Cellular Uptake of Lipophilic Inert Dinuclear Polypyridylruthenium(II) Complexes

“…[10] To date, inert dinuclear polypyridylruthenium(II) complexes have only shown modest anticancer activity. [12][13][14] While there are a variety of possible modes of binding available (e.g., intercalation, groove binding, etc. ), there are indications that the cytotoxicity of dinuclear complexes can be significantly enhanced by the incorporation of labile ligands that allow the formation of covalent adducts with DNA.…”

DNA binding properties, histidine interaction and cytotoxicity studies of water soluble ruthenium(ii) terpyridine complexes

“…+ containing different N-donor chelating ligands (N-N), such as bpy, 23,24 1,10-phenanthroline (phen), [23][24][25] 3,4,7,8-tetramethyl-1,10-phenanthroline (tmephen), 26 dipyrido(3,2-a:2′,3′-c]phenazine (dppz), 24,26 N,N,N′,N′-tetramethylethylenediamine (tmen), 23, 26 2,2′-azobispyridine (apy), 27 azpy, 28 have been prepared and studied for their DNA binding ability. It was found that most of the Ru(II)-tpy complexes are capable of binding covalently to DNA (mainly at guanine residues) forming monofunctional adducts and DNA replication was stopped by some of them.…”

Differential Anticancer Activities of the Geometric Isomers of Dinuclear Iridium(III) Complexes

“…The IC 50 results obtained for both control platinum complexes against both cell lines are consistent with previous studies. [21,28,29] While all the Cl-Irbb n complexes showed relatively poor activity against the MCF-7 cell line, the Cl-Irbb 12 and Cl-Irbb 16 complexes exhibited good activity against the MDA-MB-231 cell line. In all cases, the activity of the Cl-Irbb n complexes increased with the number of carbon atoms in the linking chain.…”