Síntese e caracterização de potenciais metalofármacos contendo ligantes azólicos contra Doença de Chagas

Abstract

Chagas disease is an illness that plagues the most vulnerable populations in emerging tropical countries, with millions of prevalent cases reported across the planet. Data indicate that if the disease is not treated properly, the chances of death are high, due to the imminent risk of heart attacks. Currently, the only chemotherapy option available is the drug Benznidazole (BZN), whose biological activity against Trypanosoma cruzi, the parasite that caused the disease, is limited or even ineffective in some cases. Furthermore, studies have shown that Fexinidazole (FXZ), a medication administered to treat sleeping sickness caused by the protozoan Trypanosoma brucei, has a good response against the parasite that transmits Chagas disease in in vivo trials. Due to the lack of a completely effective therapy for the disease, this work presents an alternative proposal based on enhancing the biological activity of a drug by coordinating it with a transition metal. In this way, 10 new metal complexes derived from Benznidazole and Fexinidazole were synthesized with the metal ions of Pt(II), Pd(II), Zn(II), Au(I) and Au(III), which were characterized by Nuclear Magnetics Resonance, Elemental Analysis, Conductimetry, Vibrational Spectroscopy in the Infrared and Raman region, UV-Vis Electronic Spectroscopy and X-ray Diffraction (for one of the structures), with the purpose of evaluating their potential biological activities against the parasite that transmits the disease of Chagas. Furthermore, computational studies were directed to investigate the possible interactions of some metal complexes synthesized with DNA using the Molecular Docking method.