Antileishmanial activity of crude extract and coumarin from Calophyllum brasiliense leaves against Leishmania amazonensis

被引:0
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作者
Mislaine Adriana Brenzan
Celso Vataru Nakamura
Benedito Prado Dias Filho
Tânia Ueda-Nakamura
Maria Claudia M. Young
Diógenes Aparício Garcia Cortez
机构
[1] Pós Graduação em Ciências Farmacêuticas,Laboratório de Microbiologia Aplicada aos Produtos Naturais e Sintéticos, Departamento de Análises Clínicas
[2] Universidade Estadual de Maringá,Departamento de Farmácia e Farmacologia
[3] Instituto de Botânica de São Paulo,undefined
[4] Universidade Estadual de Maringá,undefined
来源
Parasitology Research | 2007年 / 101卷
关键词
Coumarin; Visceral Leishmaniasis; Leishmaniasis; Cutaneous Leishmaniasis; Xanthone;
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学科分类号
摘要
Infections by protozoans of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which show renal and cardiac toxicity. As part of a search for new drugs against leishmaniasis, we evaluated the in vitro leishmanicidal activity of the (−) mammea A/BB. The compound (−) mammea A/BB is a coumarin-type mammea purified from a dichloromethane crude extract of leaves of Calophyllum brasiliense Cambess (Clusiaceae). The isolated compound was characterized using spectral analyses by UV, infrared, nuclear magnetic resonance of 1H, 13C, distortionless enhancement by polarization transfer, correlation spectroscopy, heteronuclear multiple bond correlation, and heteronuclear multiple quantum coherence. The compound (−) mammea A/BB showed significant activity against promastigote and amastigote forms of L. amazonensis, with IC50 (50% inhibition concentration of cell growth) at a concentration of 3.0 and 0.88 μg/ml and IC90 (90% inhibition concentration of cell growth) of 5.0 and 2.3 μg/ml, respectively. The coumarin (−) mammea A/BB showed no cytotoxicity against J774G8 macrophages in culture, when it was tested at high concentrations that inhibited promastigote forms. Electron microscopy studies revealed considerable ultrastructural changes when promastigote forms of L. amazonensis were treated with 3.0 μg/ml of the coumarin (−) mammea A/BB for 72 h. We observed significant changes such as mitochondrial swelling with concentric membranes in the mitochondrial matrix and intense exocytic activity in the region of the flagellar pocket. Other alterations included the appearance of binucleate cells and multiple cytoplasmic vacuolization. These results showed that (−) mammea A/BB is a potent growth inhibitor of L. amazonensis and caused important changes in the parasite’s ultrastructure. This study provided new perspectives on the development of novel drugs with leishmanicidal activity obtained from natural products.
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页码:715 / 722
页数:7
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