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 π-arene piano-stool ruthenium (II) complexes with aromatic dinitrogen chelating ligands or containing chloroquine (CQ), are described in this study: [Ru(η(6)-C10H14)(phen)Cl]PF6 (1), [Ru(η(6)-C10H14)(dphphen)Cl]PF6 (2), [Ru(η(6)-C10H14)(bipy)Cl]PF6 (3), [Ru(η(6)-C10H14)(dmebipy)Cl]PF6 (4) and [Ru(η(6)-C10H14)(bdutbipy)Cl]PF6 (5), [Ru(η(6)-C10H14)(phen)CQ](PF6)2 (6), [Ru(η(6)-C10H14)(dphphen)CQ](PF6)2 (7), [Ru(η(6)-C10H14)(bipy)CQ](PF6)2 (8), [Ru(η(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 (Kb) and the number of binding sites (n~1) were calculated using modified Stern-Volmer equations. The thermodynamic parameters ΔG at different temperatures were calculated and subsequently the values of ΔH and ΔS 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.
Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13565-905 São Carlos, SP, Brazil. Electronic address: esleg_24@hotmail.com.
Legna
L
Colina-Vegas
Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13565-905 São Carlos, SP, Brazil.
Wilmer
W
Villarreal
Instituto Nacional de Metrologia, Qualidade e Tecnologia, INMETRO, CEP 25250-020 Duque de Caxias, RJ, Brazil.
Maribel
M
Navarro
Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13565-905 São Carlos, SP, Brazil.
Clayton Rodrigues
CR
de Oliveira
Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13565-905 São Carlos, SP, Brazil.
Angélica E
AE
Graminha
Instituto de Química de São Carlos, Universidade de São Paulo, CEP 13560-970 São Carlos, SP, Brazil.
Pedro Ivo da S
PIDS
Maia
Instituto de Química de São Carlos, Universidade de São Paulo, CEP 13560-970 São Carlos, SP, Brazil.
Victor M
VM
Deflon
Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13565-905 São Carlos, SP, Brazil.
Antonio G
AG
Ferreira
Departamento de Gerontologia, Universidade Federal de São Carlos - UFSCar, CEP 13565-905 São Carlos, SP Brazil.
Marcia Regina
MR
Cominetti
Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13565-905 São Carlos, SP, Brazil. Electronic address: daab@ufscar.br.
Alzir A
AA
Batista
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms; D002417:Cattle; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002738:Chloroquine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry*; D055664:Electrochemical Techniques; D005260:Female; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008175:Lung Neoplasms; D051379:Mice; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D012428:Ruthenium / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013816:Thermodynamics
D000970:Antineoplastic Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D012710:Serum Albumin, Bovine; D012428:Ruthenium; D002738:Chloroquine; D004247:DNA; C427203:calf thymus DNA
Arene–ruthenium; BSA; Chloroquine; Cytotoxicity; DNA