Leishmanicidal Activity of (+)-Phyllanthidine and the Phytochemical Profile of Margaritaria nobilis (Phyllanthaceae)

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 12; pp. 22157 - 22169
• Main Authors: Moraes, Lienne S, Donza, Marcio R H, Rodrigues, Ana Paula D, Silva, Bruno J M, Brasil, Davi S B, Zoghbi, Maria das Graças B, Andrade, Eloísa H A, Guilhon, Giselle M S P, Silva, Edilene O
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11-12-2015; MDPI
• Subjects: alkaloid (+)-phyllanthidine; Alkaloids; Alkaloids - isolation & purification; Amastigotes; Animals; Antiprotozoal Agents - isolation & purification; Antiprotozoal Agents - pharmacology; Betulinic acid; Chromatography; Cutaneous leishmaniasis; Cytotoxicity; Dose-Response Relationship, Drug; Drugs; Euphorbiaceae - chemistry; Gallic acid; Gallic Acid - isolation & purification; Glucosides - isolation & purification; Herbal medicine; Heterocyclic Compounds, 4 or More Rings - isolation & purification; Heterocyclic Compounds, 4 or More Rings - pharmacology; Hydrolyzable Tannins - isolation & purification; Identification methods; Inhibitory Concentration 50; Kaempferol; Kaempferols - isolation & purification; Leishmania (L.) amazonensis; Leishmania braziliensis - drug effects; Leishmania braziliensis - growth & development; Leishmania braziliensis - ultrastructure; leishmanicidal activity; Life Cycle Stages - drug effects; Macrophages; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - parasitology; Male; Mammalian cells; Margaritaria nobilis; Mice; Mice, Inbred BALB C; Natural products; Nervous system; Organic chemistry; Ovarian cancer; Parasites; Parasitic diseases; Pathogens; Phytochemicals; Phytochemicals - isolation & purification; Phytochemicals - pharmacology; Plant Extracts - chemistry; Primary Cell Culture; Promastigotes; Securinega; Spectral methods; Toxicity; Triterpenes - isolation & purification; Vector-borne diseases; alkaloid (+)-phyllanthidine; Leishmania (L.) amazonensis; leishmanicidal activity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules201219829

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.