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- ItemSomente MetadadadosAntileishmanial Activity and Immunomodulatory Effects of Tricin Isolated from Leaves of Casearia arborea (Salicaceae)(Wiley-V C H Verlag Gmbh, 2017) Santos, Augusto L. [UNIFESP]; Yamamoto, Eduardo S.; Passero, Luiz Felipe D.; Laurenti, Marcia D.; Martins, Ligia F.; Lima, Marta L.; Uemi, Miriam [UNIFESP]; Soares, Marisi G.; Lago, Joao Henrique G.; Tempone, Andre G.; Sartorelli, Patricia [UNIFESP]Bioactivity-guided fractionation of antileishmanial active extract from leaves of Casearia arborea led to isolation of three metabolites: tricin (1), 1,6 '-di-O-beta-D-vanilloyl glucopyranoside (2) and vanillic acid (3). Compound 1 demonstrated the highest activity against the intracellular amastigotes of Leishmania infantum, with an IC50 value of 56 mu m. Tricin (1) demonstrated selectivity in mammalian cells (SI > 7) and elicited immunomodulatory effect on host cells. The present work suggests that tricin modulated the respiratory burst of macrophages to a leishmanicidal state, contributing to the parasite elimination. Therefore, the natural compound tricin could be further explored in drug design studies for leishmaniasis treatment.
- ItemSomente MetadadadosAntiparasitic activity and effect of casearins isolated from Casearia sylvestris on Leishmania and Trypanosoma cruzi plasma membrane(Elsevier B.V., 2014-04-15) Bou, Diego Dinis [UNIFESP]; Temporre, Andre G.; Pinto, Erika G.; Lagoa, Joao Henrique G. [UNIFESP]; Sartorellia, Patricia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Adolfo Lutz Inst; Universidade de São Paulo (USP)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.