Polypyridyl Ruthenium Complexes: Novel DNA-Intercalating Agents against Human Breast Tumor

Autor(es)

Barolli, Joao P. ^[1] ; Correa, Rodrigo S. ^[2] ; Miranda, Fabio S. ^[3] ; Ribeiro, Juliana U. ^[1] ; Bloch, Jr., Carlos ^[4] ; Ellena, Javier ^[5] ; Moreno, Virtudes ^[6] ; Cominetti, Marcia R. ^[7] ; Batista, Alzir A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Quim, CP 676, BR-13561901 Sao Carlos, SP - Brazil

^[2] Univ Fed Ouro Preto, Dept Quim, BR-35400000 Ouro Preto, MG - Brazil

^[3] Univ Fed Fluminense, Inst Quim, BR-24020141 Niteroi, RJ - Brazil

^[4] EMBRAPA Recursos Genet & Biotecnol, LEM, BR-70770917 Brasilia, DF - Brazil

^[5] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil

^[6] Univ Barcelona, Dept Quim Inorgan, Marti & Franques 1-11, E-08028 Barcelona - Spain

^[7] Univ Fed Sao Carlos, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of the Brazilian Chemical Society; v. 28, n. 10, p. 1879-1889, OCT 2017.
• Citações Web of Science: 6

Resumo

This paper describes a new series of four DNA-intercalating agents with promising anticancer activities, based on ruthenium(II) with the planar ligand dpqQX (dpqQX = dipyrido[3,2-a:2',3'-c]quinoxaline[2,3-b]quinoxaline). The complexes identified as trans-[RuCl2(dppb)(dpqQX)], cis-[RuCl2(dppb)(dpqQX)], ct-[RuCl(CO)(dppb)(dpqQX)]PF6 and ct-[RuCl2(PPh3)2(dpqQX)] (dppb = 1,4-bis(diphenylphosphine)butane and PPh3 = triphenylphosphine) were characterized by 31P{1H} nuclear magnetic resonance (NMR) and infrared spectroscopies, cyclic voltammetry, molar conductance measurements, elemental analysis, mass spectrometry and X-ray diffraction analysis for complex ct-[RuCl2(PPh3)2(dpqQX)]. Their in vitro cytotoxic activities against MDA-MB-213 and MCF-7 breast cancer cells were evaluated and compared with normal L-929 cells. Low drug concentration at which 50% of the cells are viable relative to the control (IC50) values were obtained for all four complexes compared with a reference metallodrug, cisplatin. In addition, DNA affinity studies from titrations, as well as the images obtained by atomic force microscopy (AFM) involving pBR322 plasmid DNA, suggest interactions between the metal complexes and the DNA macromolecule, in which they act as intercalating agents. The intercalation of the complexes with DNA was confirmed by viscosity measurements. (AU)

• Processo FAPESP: 13/21611-8 - Complexos de rutênio(II) coordenados a dipiridofenazinas e dipiridoquinoxalinas: ensaios celulares em linhagens de células tumorais e estudo do mecanismo de ação visando sua aplicação em terapias anticâncer
• Beneficiário: João Paulo Barolli Reis
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/06013-4 - Estudo da expressão de genes de apoptose, ciclo celular, reparo do DNA e estresse oxidativo em células de carcinoma de pulmão humano tratadas com complexos de fórmula geral [Ru(AA)(dppb)(bipy)]PF6
• Beneficiário: Alzir Azevedo Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular