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Molecules ; 20(12): 22157-69, 2015 Dec 11.
Article in English | MEDLINE | ID: mdl-26690400

ABSTRACT

The effects of the Securinega alkaloid (+)-phyllanthidine on Leishmania (L.) amazonensis and the first chemical investigation of Margaritaria nobilis L.f. (Phyllanthaceae) are described. Treating the parasites with this alkaloid caused a dose-dependent reduction in promastigote growth of 67.68% (IC50 82.37 µg/mL or 353 µM) and in amastigote growth of 83.96% (IC50 49.11 µg/mL or 210 µM), together with ultrastructural alterations in the promastigotes. No cytotoxic effect was detected in mammalian cells (CC50 1727.48 µg/mL or CC50 5268 µM). Classical chromatographic techniques and spectral methods led to the isolation and identification of betulinic acid, kaempferol, corilagin, gallic acid and its methyl ester, besides (+)-phyllanthidine from M. nobilis leaves and stems. Margaritaria nobilis is another source of the small group of Securinega alkaloids, together with other Phyllanthaceae (Euphorbiaceae s.l.) species. The low toxicity to macrophages and the effects against promastigotes and amastigotes are suggestive that (+)-phyllanthidine could be a promising antileishmanial agent for treating cutaneous leishmaniasis.


Subject(s)
Antiprotozoal Agents/pharmacology , Euphorbiaceae/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Leishmania braziliensis/drug effects , Life Cycle Stages/drug effects , Phytochemicals/pharmacology , Alkaloids/isolation & purification , Animals , Antiprotozoal Agents/isolation & purification , Dose-Response Relationship, Drug , Gallic Acid/isolation & purification , Glucosides/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Hydrolyzable Tannins/isolation & purification , Inhibitory Concentration 50 , Kaempferols/isolation & purification , Leishmania braziliensis/growth & development , Leishmania braziliensis/ultrastructure , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/parasitology , Male , Mice , Mice, Inbred BALB C , Pentacyclic Triterpenes , Phytochemicals/isolation & purification , Plant Extracts/chemistry , Primary Cell Culture , Triterpenes/isolation & purification , Betulinic Acid
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