Complexos de rutênio(II) com potenciais atividades antitumorais: síntese, caracterização e ensaios biológicos

Abstract

In this thesis phosphinic ruthenium complexes coordinated to ligands of biological interest: folic acid, 6-mercaptopurine, 2-mercaptopyridine and 8-aminoquinoline, dpqQX, dppz and dpq (dipyridophenazine and derivatives) mainly, were synthesised from the precursor complexes [RuCl2(PPh3)3], [RuCl2(dppb)(PPh3)] and cis- [RuCl2(dppb)(bipy)] and characterized by the usual techniques: 1H, 31P{1H} and 13C{1H}, IR, UV-Vis, molar conductimetry, elemental analysis, cyclic and differential pulse voltammetry, mass spectrometry and X ray diffraction of single crystal when applicable. The synthesized complexes showed values of E1/2 larger than their corresponding precursors, and in the case of complexes with folic acid presented irreversibility in the oxidation of ruthenium. Molar conductance measurements and elemental analysis corroborated the proposed formulae and the study of crystals solved by X ray diffraction confirmed the expected structures. The complexes (series I-III) were evaluated in vitro against MDA-MB-231 and MCF7 breast cancer cell beyond in mouse fibroblast cells. The Ru-FO complexes (series I) has been activity against breast cancer cells MDA-MB-231, suggesting that small structural modifications presented variation in cytotoxic activity. The ruthenium complexes coordinated to dpqQX, dppz and dpq ligands (series II) were very active and selective against breast cancer cells studied. Studies of their Interaction with ct-DNA confirmed the existence of interaction by intercalation mainly of these complexes (series II).