Compostos carbonílicos heterobimetálicos de Ru(II)/Fe(II) : propriedades citotóxicas e estudo da interação com BSA e DNA
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2016-03-30Autor
Dávila Rodríguez, María José
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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.