RESUMO

Seven benzo[c]phenanthridines, synthetic or isolated from Zanthoxylum rhoifolium root bark, were evaluated against Leishmania amazonensis axenic amastigotes. Five of them were considered leishmanicidal, with IC50 values ranging from 0.03 to 0.54 µM, and were evaluated on intramacrophagic amastigotes of L. amazonensis. Chelerythrine displayed the best activity (IC50=0.5 µM), which was in the same range as the reference compound amphotericin B (IC50=0.4 µM). In vivo studies with chelerythrine, avicine, and fagaridine on a model of mice cutaneous leishmaniasis resulted in the identification of fagaridine as the most active compound. Fagaridine decreased the parasitic burden more than 50% at the 3rd and 6th weeks after the end of treatment.

Assuntos

Leishmania/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Fenantridinas/farmacologia , Extratos Vegetais/farmacologia , Zanthoxylum/química , Animais , Benzofenantridinas/química , Benzofenantridinas/isolamento & purificação , Benzofenantridinas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Concentração Inibidora 50 , Leishmaniose Cutânea/parasitologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Fenantridinas/química , Fenantridinas/isolamento & purificação , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Plantas Medicinais