Cytotoxicity of Ru(II) piano-stool complexes with chloroquine and chelating ligands against breast and lung tumor cells: Interactions with DNA and BSA

The synthesis and spectroscopic characterization of nine pi-arene piano-stool ruthenium (II) complexes with aromatic dinitrogen chelating ligands or containing chloroquine (CQ), are described in this study: [Ru(eta(6)-C10H14)(phen)Cl]PF6 (1), [Ru(eta(6)-C10H14)(dphphen)Cl]PF6 (2), [Ru(eta(6)-C10H14)(bipy)Cl]PF6 (3), [Ru(eta(6)-C10H14)(dmebipy)Cl]PF6 (4) and [Ru(eta(6)-C10H14)(bdutbipy)Cl]PF6 (6), [Ru(eta(6)-C10H14)(phen)CQ]PF6)(2) (6), [Ru(eta(6)-C10H14)(dphphen)CQ]PF6)(2) (7), [Ru(eta(6)-C10H14)(bipy)CQ]PF6)(2) (8), [Ru(eta(6)-C10H14)(dmebipy)CQ](PF6)(2) (9): [1,10-phenanthroline (phen), 4,7-diphenyl-1,10-phenanthroline (dphphen), 2,2'-bipyridine (bipy), 5,5'-dimethyl-2,2'-bipyridine (dmebipy), and 4,4'-di-t-butyl-2,2'-bipyridine (dbutbipy)]. The solid state structures of five ruthenium complexes (1-5) were determined by X-ray crystallography. Electrochemical experiments were performed by cyclic voltammetry to estimate the redox potential of the Ru-II/Ru-III couple in each case. Their interactions with DNA and BSA, and activity against four cell lines (L929, A549, MDA-MB-231 and MCF-7) were evaluated. Compounds 2, 6 through 9, interact with DNA which was comparable to the one observed for free chloroquine. The results of fluorescence titration revealed that these complexes strongly quenched the intrinsic fluorescence of BSA following a static quenching procedure. Binding constants (K-b) and the number of binding sites (n similar to 1) were calculated using modified Stem-Volmer equations. The thermodynamic parameters Delta G at different temperatures were calculated and subsequently the values of Delta H and Delta S were also calculated, which revealed that hydrophobic and electrostatic interactions play a major role in the BSA-complex association. The MTT assay results indicated that complexes 2,5 and 7 showed cytostatic effects at appreciably lower concentrations than those needed for cisplatin, chloroquine and doxorubicin. (C) 2015 Elsevier Inc. All rights reserved.