title: Leishmanicidal Activity of (+)-Phyllanthidine and the Phytochemical Profile of Margaritaria nobilis (Phyllanthaceae).
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.
authors.affiliation: Laboratório de Parasitologia e Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará 66075-110, Brazil. liennemoraes@hotmail.com.|Instituto Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil. liennemoraes@hotmail.com.
authors.forename: Lienne S
authors.initials: LS
authors.lastname: Moraes
authors.affiliation: Programa de Pós-Graduação em Química, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, Pará 66075-110, Brazil. marciodonza@hotmail.com.
authors.forename: Marcio R H
authors.initials: MR
authors.lastname: Donza
authors.affiliation: Instituto Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil. anarodrigues@iec.pa.gov.br.|Laboratório de Microscopia Eletrônica, Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde, Belém, Pará 66090-000, Brazil. anarodrigues@iec.pa.gov.br.
authors.forename: Ana Paula D
authors.initials: AP
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Parasitologia e Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará 66075-110, Brazil. bjmartins@ufpa.br.|Instituto Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil. bjmartins@ufpa.br.
authors.forename: Bruno J M
authors.initials: BJ
authors.lastname: Silva
authors.affiliation: Programa de Pós-Graduação em Química, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, Pará 66075-110, Brazil. davibb@ufpa.br.
authors.forename: Davi S B
authors.initials: DS
authors.lastname: Brasil
authors.affiliation: Coordenação de Botânica, Museu Paraense Emílio Goeldi, Belém, Pará 66077-901, Brazil. gracazoghbi@gmail.com.
authors.forename: Maria das Graças B
authors.initials: Md
authors.lastname: Zoghbi
authors.affiliation: Programa de Pós-Graduação em Química, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, Pará 66075-110, Brazil. eloisandrade@ufpa.br.|Coordenação de Botânica, Museu Paraense Emílio Goeldi, Belém, Pará 66077-901, Brazil. eloisandrade@ufpa.br.
authors.forename: Eloísa H A
authors.initials: EH
authors.lastname: Andrade
authors.affiliation: Programa de Pós-Graduação em Química, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, Pará 66075-110, Brazil. giselle@ufpa.br.
authors.forename: Giselle M S P
authors.initials: GM
authors.lastname: Guilhon
authors.affiliation: Laboratório de Parasitologia e Biologia Estrutural, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará 66075-110, Brazil. edilene@ufpa.br.|Instituto Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil. edilene@ufpa.br.
authors.forename: Edilene O
authors.initials: EO
authors.lastname: Silva
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification; D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019665:Euphorbiaceae / Q000737:chemistry*; D005707:Gallic Acid / Q000302:isolation & purification; D005960:Glucosides / Q000302:isolation & purification; D006576:Heterocyclic Compounds, 4 or More Rings / Q000302:isolation & purification / Q000494:pharmacology*; D047348:Hydrolyzable Tannins / Q000302:isolation & purification; D020128:Inhibitory Concentration 50; D044949:Kaempferols / Q000302:isolation & purification; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D008018:Life Cycle Stages / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053978:Pentacyclic Triterpenes; D064209:Phytochemicals / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry; D061251:Primary Cell Culture; D014315:Triterpenes / Q000302:isolation & purification; D000094062:Betulinic Acid
chemical_list: D000470:Alkaloids; D000981:Antiprotozoal Agents; D005960:Glucosides; D006576:Heterocyclic Compounds, 4 or More Rings; D047348:Hydrolyzable Tannins; D044949:Kaempferols; D053978:Pentacyclic Triterpenes; D064209:Phytochemicals; D010936:Plant Extracts; D014315:Triterpenes; C503182:ent-phyllanthidine; C049096:corilagin; D005707:Gallic Acid; C006552:kaempferol; D000094062:Betulinic Acid
keywords: Leishmania (L.) amazonensis; alkaloid (+)-phyllanthidine; leishmanicidal activity