Atividade antimalárica in vitro de extratos, frações e substâncias isoladas de duas espécies vegetais da Amazônia

Abstract

Malaria remains one of the world’s leading infectious diseases, the spread of Plasmodium strains resistant to available therapies has threatened disease control measures, which have seen an increase in cases. In the search for more effective therapies to combat the disease, plants used in traditional medicine have been investigated, since the substances that originated the current antimalarials were isolated from medicinal plants. The present work is an investigation of the in vitro antimalarial activity of extracts of the Brazil nut tree (Bertholletia excelsa Bonpl.), fractions and indole alkaloids isolated from carapanaúba (Aspidosperma excelsum Benth.), in a search for potentially new antimalarials. B. excelsa extracts were prepared from residual materials from plantations in the municipality of Itacoatiara, Amazonas State, by maceration in organic solvents and water. The methanol extract of the bark, as well as fractions and alkaloids isolated from the methanolic extract of the A. excelsum bark were donated by a doctoral student project in the area of natural products chemistry at LAPAAM (Amazon Active Principles Laboratory). The antimalarial activity was evaluated using the in vitro microtest using synchronized cultures of the K1 strain (resistant to chloroquine) of Plasmodium falciparum. To evaluate selectivity, the in vitro toxicity of substances to a normal human fibroblast lineage (MRC-5) was evaluated using the Alamar Blue bioassay. Seventy extracts of B. excelsa were prepared and submitted to an initial screening to classify antimalarial activity. Of these, the methanol extracts exhibited better yields and the ethanol extract of the stem bark showed better activity, with IC50 < 1.00 µg/mL, and the antiplasmodial activity of the roots and branches of the plant is also reported here. For A. excelsum, the methanol extract of the bark (IC50 5.24 µg/mL), four alkaloid-enriched fractions and eight indole alkaloids (IC50 10.3-78.9 µM) were evaluated against P. falciparum, with low toxicity against human fibroblasts.