Síntese e caracterização de complexos de fármacos antimaláricos coordenados a Cu(II), Zn(II) e Ag(I). Estudo de seus possíveis mecanismos de ação e avaliação de sua atividade antimalárica.

Abstract

Malaria is the parasitic disease with the highest morbidity and mortality in the world, due to the parasite’s resistance to the most successful drug, chloroquine. Therefore, there are several studies searching for new drugs and alternative treatments. Researchers have been putting effort on a new strategy, which is the combination of a transition metal with an organic biomolecule, to develop metallo-drugs with improved biological activity. The strategy behind this is well known as synergic effect. Thus, in this work, we present the synthesis and characterization of metal complexes based on Cu(II), Zn(II) and Ag(I) with the antimalarial drugs amodiaquine (AQ) and primaquine (PQ). The characterizations performed were followed by elemental analysis of carbon, hydrogen and nitrogen (CHN), molar conductivity, infrared absorption spectroscopy, ¹H, ¹³C and ³¹P nuclear magnetic resonance (NMR) and UV-Visible absorption spectroscopy. Interactions of metal complexes synthesized with hemin and DNA were also evaluated, in order to estimate the magnitude of their interaction between these targets and the metallodrug. Compounds ZnAQCl2 and ZnAQ(OH)2 were evaluated against sensitive and resistant strains of Plasmodium falciparum and the results showed that these compounds have promising activity to eradicate malaria parasites. ZnAQ(OH)2 complex displayed IC50 in the nanomolar concentration range, which encourage us to continue with the in vivo antimalarial activity studies.