Antiparasitic activity and effect of casearins isolated from Casearia sylvestris on Leishmania and Trypanosoma cruzi plasma membrane

Autor(es)

Bou, Diego Dinis ^[1] ; Temporre, Andre G. ^[2] ; Pinto, Erika G. ^{[2, 3]} ; Lagoa, Joao Henrique G. ^[1] ; Sartorellia, Patricia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP - Brazil

^[2] Adolfo Lutz Inst, Dept Parasitol, BR-01246000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Med Trop Sao Paulo, BR-05403000 Silo Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Phytomedicine; v. 21, n. 5, p. 676-681, APR 15 2014.
• Citações Web of Science: 19

Resumo

Leishmaniasis and Chagas disease are infectious diseases caused by parasite Leishmania sp. and Trypanosoma cruzi, respectively, and are included among the most neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antiparasitic potential of MeOH extract from leaves of Casearia sylvestris Sw. (Salicaceae), a bioguided fractionation was conducted and afforded four active clerodane diterpenes (casearins A, B, G, and J). The obtained results indicated a superior efficacy of tested casearins against trypomastigotes of T. cruzi, with IC50 values ranging from 0.53 to 2.77 mu g/ml. Leishmania infantum promastigotes were also susceptible to casearins, with IC50 values in a range between 4.45 and 9.48 mu g/ml. These substances were also evaluated for mammalian cytotoxicity against NOV cells resulting in 50% cytotoxic concentrations (CC50) ranging from 1.46 to 13.76 mu g/ml. Additionally, the action of casearins on parasite membranes was investigated using the fluorescent probe SYTOX Green. The obtained results demonstrated a strong interaction of casearins A and B to the plasma membrane of T. cruzi parasites, corroborating their higher efficacy against these parasites. In contrast, the tested casearins induced no alteration in the permeability of plasma membrane of Leishmania parasites, suggesting that biochemical differences between Leishmania and T. cruzi plasma membrane might have contributed to the target effect of casearins on trypomastigotes. Thus, considering the importance of studying novel and selective drug candidates against protozoans, casearins A, B, G, and J could be used as tools to future drug design studies. (c) 2014 Elsevier GmbH. All rights reserved. (AU)

• Processo FAPESP: 11/51739-0 - Uso sustentável da biodiversidade de áreas remanescentes da Mata Atlântica do Estado de São Paulo: avaliação, isolamento e caracterização molecular de metabólitos secundários bioativos em espécies vegetais
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular
• Processo FAPESP: 13/16320-4 - Prospecção de metabólitos anti-parasitários e anti-tumorais de espécies vegetais da Mata Atlântica
• Beneficiário: Patricia Sartorelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular