Journal
MOLECULES
Volume 20, Issue 12, Pages 22157-22169Publisher
MDPI
DOI: 10.3390/molecules201219829
Keywords
Leishmania (L.) amazonensis; leishmanicidal activity; alkaloid (+)-phyllanthidine
Funding
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [573767/2008-4]
- FAPESPA (Fundacao Amazonia de Amparo a Estudos e Pesquisas do Para)
- INBEB (Instituto Nacional de Biologia Estrutural e Bioimagem)
- PROPESP (Pro-reitoria de Pesquisa)/Universidade Federal do Para
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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 g/mL or 353 mu M) and in amastigote growth of 83.96% (IC50 49.11 g/mL or 210 mu M), together with ultrastructural alterations in the promastigotes. No cytotoxic effect was detected in mammalian cells (CC50 1727.48 mu g/mL or CC50 5268 mu M). 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.
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