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The in vitro antiproliferative effects of 4 neolignans purified from the ethyl-acetate extract from leaves of Piper regnellii (MIQ.) C. DC. var. pallescens (C. DC.) YUNCK against Trypanosoma cruzi were investigated. These isolated compounds were identified through spectral analyses of UV, EI-MS, 1 H-, 13 C-NMR, H-H COSY, gNOE, HETCOR, and HMBC. The compounds eupomatenoid-5, eupomatenoid-6, and conocarpan showed considerable activity against epimastigote forms of T. cruzi, with 50% inhibition concentrations (IC 50 ) of 7.0, 7.5, and 8.0 m mg/ml respectively. After methylation, these compounds showed a lessened inhibitory activity to the growth of the protozoan, suggesting that loss of the hydroxyl group from their molecules reduces the activity. The compound eupomatenoid-3 showed lower activity than the hexane fraction. Eupomatenoid-5 was significantly more active than benznidazole, the antiparasitic drug of choice for treatment of Chagas' disease. The crude extract, hexane fraction, and eupomatenoid-5 caused no lysis in sheep blood at concentrations which inhibit the growth of epimastigote forms. The compound eupomatenoid-5 showed low cytotoxic effects against Vero cells. These results provide new perspectives on the development of novel drugs obtained from natural products with trypanocidal activity. However, the extracts and active compound isolated from P. regnellii var. pallescens should be further studied in animal models for in vivo efficacy.

"Antileishmanial activity of hydroalcoholic extract and fractions obtained from leaves of Piper regnellii (Miq.) C. DC. var. pallescens (C. DC.)". Biological activity of the crude extract and several fractions obtained from Piper regnellii var. pallescens was assessed on Leishmania amazonensis. This study included the extraction process and bioassayguided fractionation by the adsorption chromatography method. A progressive increase in the antileishmanial effect was observed in the course of the purifi cation process. The hydroalcoholic extract water soluble (EBA) had a 50% inhibitory concentration (IC 50 ) at 167 μg/mL whereas the hydroalcoholic extract acetate soluble (EBAcOEt) showed an IC 50 of 30 μg/mL against the growth of promastigote forms after 48 h of culturing. The hexan fraction (FHex) showed an antileishmanial activity greater than EBAcOEt with IC 50 at 21.5 μg/mL. Analysis of cytotoxicity indicated that the toxic concentrations of the EBA, EBAcOEt, and fractions were higher for J774G8 macrophages than for the protozoans.

Eupomatenoid-5, a compound isolated from leaves of Piper regnellii var. pallescens, showed antiprotozoal activity against the epimastigote proliferative stages and intracellular amastigote forms of Trypanosoma cruzi Y strain. Eupomatenoid-5, at 7.0 microg/ml (50% growth inhibition concentration) produced morphological changes in epimastigote forms of the parasite, such as intense cytoplasmic vacuolization, mitochondrial swelling, kinetoplast alteration, presence of myelin-like figures, and mitochondrial damage, as observed by transmission electron microscopy. In amastigote forms in LLCMK(2) cells, at 7.0-microg/ml concentration, the compound induced a decrease in the number of cells with internalized parasites and in the number of internalized parasites per LLCMK(2) cell, compared with untreated cells. Furthermore, intense cytoplasmic vacuolization and autophagic vacuoles were observed in T. cruzi intracellular amastigotes after 72 h of incubation. Scanning electron microscopy confirmed the alterations in the shape of the parasites.

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