Síntese e caracterização de complexos de zinco e cobre contendo ligantes azólicos: estudos de interação com DNA e avaliação de suas atividades antiparasitárias e antifúngicas

Abstract

Several studies have described the use of imidazoles and triazoles derivatives as synthetic alternatives in the treatment of diseases such as Leishmaniasis and Sporotrichosis, since the drugs used against these diseases are quite cytotoxic to the host, besides the resistance developed by the parasite or fungus to such drugs. In order to improve the biological activities of these compounds, the synergistic effect resulting from the combination of these derivatives imidazoles and triazoles (ketoconazole (KTZ), clotrimazole (CTZ), itraconazole (ITZ) e fluconazole (FLZ))with transition metal íons such as copper(II) and zinc(II), essential for our organism, is used. In this work, synthesis and characterization of eighteen metal complexes and six coordination polymers of Cu(II) and Zn(II) from complexation reactions of imidazoles and triazoles were carried out with the salts of interest. The obtained compounds were characterized by infrared (IR) and ultraviolet-visible (UV-Vis) spectroscopies (except C19-C24), mass (ESI-MS) (Except C7-C12), nuclear magnetic resonance (RMN) of 1H and 13C, and elemental analysis of carbon, hydrogen and nitrogen (CHN) and X-ray crystallography. The metal complexes were obtained in moderate yields (39-94%) and their structures were proposed based on the analysis of all spectroscopic and analytical data and, in the case of the complexes C7, C10 and polymers C20, C22, C23 and C24, by the elucidation of the crystal structure from x-ray studies. Based on these analyzes, it was proposed that these compounds present tetrahedral geometry (except complex C10), coordinated to the metal ion, presenting the ligands (KTZ, CTZ and ITZ) and the auxiliary ligands (chloride, nitrate, acetate) in the monodentate mode and FLZ in the bidentate mode. The series of these compounds containing KTZ, CTZ and ITZ have been for the analysis of their activities against the causative parasites of both the diseases proposed here and also other diseases. Preliminary results showed that Zn-ITZ complexes has very promising activities against the parasites Leishmania amazonensis, the fungi Sporothrix brasiliensis and Sporothrix schenckii, which may lead to the continuation of their studies.