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

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Abstract

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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Authors and Affiliations

  1. Pós Graduação em Ciências Farmacêuticas, Maringá, PR, Brazil

    Mislaine Adriana Brenzan

  2. Laboratório de Microbiologia Aplicada aos Produtos Naturais e Sintéticos, Departamento de Análises Clínicas, Universidade Estadual de Maringá, Maringá, PR, Brazil

    Celso Vataru Nakamura, Benedito Prado Dias Filho & Tânia Ueda-Nakamura

  3. Instituto de Botânica de São Paulo, Maringá, PR, Brazil

    Maria Claudia M. Young

  4. Departamento de Farmácia e Farmacologia, Universidade Estadual de Maringá, Av. Colombo 5790, 87020-900, Maringá, PR, Brazil

    Diógenes Aparício Garcia Cortez

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  1. Mislaine Adriana Brenzan
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  2. Celso Vataru Nakamura
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  3. Benedito Prado Dias Filho
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  4. Tânia Ueda-Nakamura
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  6. Diógenes Aparício Garcia Cortez
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Correspondence to Diógenes Aparício Garcia Cortez.

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Brenzan, M.A., Nakamura, C.V., Prado Dias Filho, B. et al. Antileishmanial activity of crude extract and coumarin from Calophyllum brasiliense leaves against Leishmania amazonensis . Parasitol Res 101, 715–722 (2007). https://doi.org/10.1007/s00436-007-0542-7

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