Avaliação da atividade leishmanicida de Annona mucosa, A. sericea e Ephedrantus amazonicus frente a Leishmania amazonensis, L. braziliensis e L. guyanensis

Abstract

Leishmaniasis is a zoonotic infectious disease caused by protozoa of the Leishmania genus, widely distributed in tropical and subtropical regions. Constitutes a growing public health problem, and is considered one of the endemic diseases of priority interest. Due to dificults to application and toxicity found in the treatment with commercial drugs, a great number of botanic species is investigated as alternative sources of antileishmanial substances. In this context the Annonaceae family possesses highlighted several species are potentially bioactive molecules. Then, the species Annona mucosa, Annona sericea and Ephedranthus amazonicus were evaluated in vitro in cultures of promastigotes of Leishmania spp. The organic extracts of A. mucosa showed activity against L. amazonensis, with inhibitory concentration of 50% (IC50) between 9.32 - 46.54 μg.mL-1; against L. braziliensis, with IC50 between 27.42 - 170.15 μg.mL-1 and against L. guyanensis with IC50 of 16.23 - 165.02 μg.mL-1. The organic extracts of A. sericea were tested against L. amazonensis and L. braziliensis showing, IC50 between 0.40 - 55.86 μg.mL-1 against L. amazonensis and IC50 between 86.21 - 151.82 μg.mL-1 against L. braziliensis. The organic extracts of E. amazonicus were tested against L. amazonensis and L. braziliensis presenting, IC50 between 2.47 - 2.57 μg.mL-1 against L. amazonensis and IC50 of 265.45 μg.mL-1 against L. braziliensis. From do dichlorometane leaves extract was isolated two alkaloids identified as liriodenine (1) and atherospermidine (2). The alkaloid liriodenine, major alkaloid isolated from this extract, showed activity against L. amazonensis, L. braziliensis and L. guyanensis, being observed, respectively, IC50 of 1.43, 55.92 and 0.84 μg.mL-1. On the basis of the results obtained and due to better perspective to cultivate, the species A. mucosa was selected for evaluation in vitro against amastigotes of L. amazonensis. The alkaloid liriodenine and organic extracts of A. mucosa were active against intracellular amastigotes of L. amazonensis observed reduction of 80% of infected macrophages and elimination of 70% of intracellular amastigote. Dichloromethane and hexane extract of leaves of A. mucosa were selected for evaluation in vivo the treatment of experimental cutaneous leishmaniasis in BALB/c mice caused by L. amazonensis. The bases of ointments formulated extracts were effective in treating skin injury in both topical application and in intraperitoneally. Results are very promising and stimulate the continuation of the studies on A. mucosa to aim for the elaboration of a potential leishmanicidal product.