Compostos carbonílicos heterobimetálicos de Ru(II)/Fe(II) : propriedades citotóxicas e estudo da interação com BSA e DNA

Abstract

Ruthenium and iron-based drugs are an option for the development of improved chemotherapeutic agents for cancer treatment with lower toxicity. Thereby, this work present the in vitro cytotoxic activity and in vitro interaction studies of Calf-Thymus DNA (CT-DNA) and bovine serum albumin (BSA) with the synthetized carbonyl heterobimetallic compounds of Ru(II)/Fe(II) with general formula ct-[RuCl(CO)(N-N)(dppf)]PF6, with N-N = 1,10-phenantrholine (phen, 1); dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq, 2); dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3); dipyrido[3,2-f:2′,3′-h]quinoxalino[2,3-b]quinoxaline (dpqQX, 4) and dppf = 1,1’-bis(diphenylphosphino)ferrocene. Spectroscopy (IR, UV-vis and 1H-13C{1H}- and 31P{1H}-NMR) and voltammetry techniques along with elemental analysis were employed for the characterization of the complexes. Spectrofluorimetric titrations shows strong and spontaneous interactions of 1–3 with BSA through a static quenching mechanism resulting in binding constants in the order of 104 - 106 L·mol-1 at 310 K. Viscosity measurements and circular dichroism spectra prompts interactions of 1–4 with CT-DNA via non-classical intercalations or by an electrostatic pathway. MTT assays in cell lines MDA-MB-231 and V79-4 revealed IC50 values at range of 0,19 – 1,11 µmol·L-1 and 1,29 – 3,85 µmol·L-1 respectively, after 48 h of exposure to 1–4. However, stability studies of solutions 1 mmol·L-1 of 1–4 in DMSO shows their rapid reaction with this solvent.