Atividade biológica in vitro de complexos de cobre e zinco com derivados vanilóides: caracterização, ensaio de geração de superóxido, atividades anticâncer e antiparasitária

Abstract

Metallic compounds containing vanilloid derivatives have gained interest in medicinal inorganic chemistry, due to the biological properties of this class of ligands, such as the ability to generate reactive oxygen species (ROS). Additionally, the coordination of these ligands with bioactive metallic centers, such as copper and zinc, has been a strategy used to obtain more effective drugs with fewer side effects. In this context, the present work aims to synthesize and characterize complexes of the type [M(phen)(L)2], where M=Cu2+ and Zn2+, and L=o-vanillin (ovan) and o-vani, in which the latter is a schiff base derived from the reaction of o-vanillin with isoniazid. In addition, the synthesized complexes will be tested against cervical (HeLa) and gastric cancer (AGS) strains, as well as the evaluation of their antiparasitic activity against Y strains of T. Cruzi. From the vibrational spectra of the complexes [M(phen)(ovan)2], the mode of coordination of the ovan was determined by the variation of the energies of the carbonyl bands, in addition, for the compounds [M(phen)(ovani)2], the presence of the hydrazide C=O bands at 1709 cm-1 and the imine band (C=N) around 1630 cm-1 , in the vibrational spectra, indicated the formation of the Schiff base. In the study of cyclic voltammetry, it was observed that [Cu(phen)(ovan)2] presented an E1/2 of -171 mV, which is within the redox range of the biological medium. Thus, a nitroblue tetrazolium chloride (NBT) test was performed, using glutathione as a reducing agent, showing a positive response for the formation of O2 - . The compounds [M(phen)(ovan)2] were active against the HeLa and AGS strains, with the Cu2+ complex showing greater efficiency in both strains with IC50 of 6.19 (HeLa) and 5.63 µM (AGS ). In relation to antiparasitic activity, the two complexes [Cu(phen)(ovan)2] and [Zn(phen)(ovan)2], were able to inhibit the growth of Y strains of T. Cruzi in the epimastigote form, presenting 100% and 66% inhibition respectively. The antiparasitic activity of the Cu2+ compound was higher and presented an IC50 of 5.03 µM against 108 µM of the Zn2+ complex.