Síntese, atividade biológica e estudos de interação com biomoléculas de complexos metálicos de ligantes com interesse farmacológico

Abstract

In the present work eight metal complexes were studied being four already related in the literature and, four new complexes. The new complexes were characterized using physicochemical and spectroscopic techniques: [CuCl2(H2O)(NOR)].H2O (1), [CuCl2(py)(NOR)].H2O(2), [CuCl(bipy)(NOR)]Cl.2H2O (3), [CuCl2(phen)(NOR)].3H2O (4), [AuS(CH3)2(NOR)]Cl (5), [Au(pyc)(NOR)2]2Cl.3H2O (6), [CuCl(L1)(phen)].0.5H2O (7) and [CuCl(L2)(phen)].2.5H2O (8),where NOR is the fluoroquinolone antibiotic norfloxacin, py = pyridine, bipy = 2,2- bipyridine, phen = 1,10-phenantroline, pyc = piridin-2-carboxilic acid and L1 and L2 represent the Schiff bases 2-((5-nitrofuran-2-il)metilamino)fenol and 2-(4-nitrobenzilidenoamino) fenol. Complexes 3, 4 and 7 showed promising activity against Tripanossoma cruzi, the causative agent of Chagas disease (0.94 - 16 µmol L-1), whereas 1-6 proved to be active againstdifferent bacteria strains. In some cases, however, the free NOR demonstrated superior activity. Complexes 7 and 8 were active against seven cancer cell lines in doses lower than 2 µg mL-1 (or 3.4 µmol L-1), whilst 7 also showed antifungal activity in some fungi strains.Complexes 1-8 interacted with DNA on a scale of weak to moderate (Kb 103-104). The interaction of complexes 1, 7 and 8 with DNA, which was perhaps due to intercalation, whilst the other complexes probably interacted with the DNA's external structure. Complexes 1-4, 7 and 8 Interacted with the bovine (BSA) and human (HSA) serum albumins.These interactions were moderate and occurred, at least in part, through a static mechanism. Complexes 5 and 6 interacted with HSA through a mainly dynamic and static mechanism respectively. The negative values of Gibbs free energy ([delta]G) showed that 5 and 6 interacted spontaneously with HSA.