RESUMO
Bioguided fractionation of extract from the leaves of Aristolochia cymbifera led to the isolation of the furofuran lignans fargesin, epieudesmin, and sesamin; the dibenzylbutyrolactone lignans hinokinin and kusunokinin; and an ENT-labdane diterpene named copalic acid. Our data demonstrated that copalic acid and kusunokinin were the most active compounds against trypomastigotes of Trypanosoma cruzi. Additionally, copalic acid demonstrated the highest parasite selectivity as a result of low toxicity to mammalian cells, despite a considerable hemolytic activity at higher concentrations. Among the isolated compounds, kusunokinin could be considered the most promising candidate, as it displayed significant activity against intracellular amastigotes (IC(50) = 17 µM) and trypomastigotes (IC(50) = 51 µM) without hemolytic activity. Fargesin, hinokinin, epieudesmin, and sesamin were also effective against trypomastigotes, but these compounds were highly toxic to mammalian cells and no parasite selectivity could be identified. The need for novel drugs for American trypanosomiasis is evident, and these secondary metabolites from A. cymbifera represent a useful tool for drug design.
Assuntos
Aristolochia/química , Doença de Chagas/tratamento farmacológico , Diterpenos/uso terapêutico , Lignanas/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Animais , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Hemolíticos/efeitos adversos , Concentração Inibidora 50 , Lignanas/isolamento & purificação , Lignanas/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Tripanossomicidas/isolamento & purificação , Tripanossomicidas/farmacologiaRESUMO
The fractionation through bioguided antileishmanial activity of the dichloromethane extract of Cassia fistula fruits (Leguminosae) led to the isolation of the active isoflavone biochanin A, identified by spectroscopic methods. This compound showed 50% effective concentration (EC(50)) value of 18.96 microg/mL against promastigotes of Leishmania (L.) chagasi. The cytotoxicity of this substance against peritoneal macrophages resulted in an EC(50) value of 42.58 microg/mL. Additionally, biochanin A presented an anti-Trypanosoma-cruzi activity, resulting in an EC(50) value of 18.32 microg/mL and a 2.4-fold more effectiveness than benznidazole. These results contribute with novel antiprotozoal compounds for future drug design studies.
