Complexos de Ru(II): síntese, caracterização e reatividade de potenciais vasodilatadores

Abstract

Cardiovascular disease is a leading cause of death in the world and one of the factors contributing to this is associated with production and action of cyclic guanosine 3'-5'-monophosphate (cGMP) in a biological environment. Recent studies indicate that organic compounds such as YC-1 and BAY class, are able to act on the vasodilatation Once the performance of these organic compounds is dependent on the indole and azaindole rings and knowing they contain nonbonding pair of electrons, a series of complex type cis-[RuCl(L)(X-X)2]+wherein L is quinoline, 1H-indazole, 1H-indazole-6-caboxyaldehyde, 1Hbenzimidazole, 4-azaindole, 5-azaindole, or 7-azaindole, whereas X-X is 2,2-bipyridine or 1,10-phenanthroline, was prepared. The synthesis and characterization of these complexes was performed using elemental analysis, nuclear magnetic resonance spectroscopy, molecular absorption spectroscopy in the ultraviolet-visible, vibrational spectroscopy in the infrared region and conductivity and cyclic voltammetry supporting the formulation and purity of these compounds. Light irradiation data at 300 nm and 420 nm indicated these complexes are photosensitive. Furthermore, such complexes are capable of reacting with superoxide ion (IC50 in the range of 45 to 86 mmol L-1), this behavior that allows the complex to act as antioxidants. There is evidence that the complexes interact with bovine serum albumin, which might improve bioavailability of the drug. Vasodilation assays indicated that these complexes (IC50 between 55 and 700 nmol L-1) are efficient in rat aortic rings when compared to free ligands (IC50 between 560 and 8500 nmol L-1) and BAY-412 272 (IC50 440 nmol L-1). Moreover, assay carried out with the complex cis-[RuCl(5- ain)(bpy)2] + shows that it contributes to increase production of cGMP (about 600fmol per mg protein-1 ), indicative that this complex may be stimulating the activation of soluble guanylate cyclase (sGC) or inhibiting phosphodiesterase (PDE). Therefore, the overall data showed novel strategy is suitable to prepare pharmaceutical compounds for cardiovascular disease.