title: Antiparasitic activity and effect of casearins isolated from Casearia sylvestris on Leishmania and Trypanosoma cruzi plasma membrane.
abstract: 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 μg/ml. Leishmania infantum promastigotes were also susceptible to casearins, with IC50 values in a range between 4.45 and 9.48 μg/ml. These substances were also evaluated for mammalian cytotoxicity against NCTC cells resulting in 50% cytotoxic concentrations (CC50) ranging from 1.46 to 13.76 μg/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.
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270 Diadema, SP, Brazil.
authors.forename: Diego Dinis
authors.initials: DD
authors.lastname: Bou
authors.affiliation: Departamento de Parasitologia, Instituto Adolfo Lutz, 01246-000 São Paulo, SP, Brazil.
authors.forename: André G
authors.initials: AG
authors.lastname: Tempone
authors.affiliation: Departamento de Parasitologia, Instituto Adolfo Lutz, 01246-000 São Paulo, SP, Brazil; Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470, 05403-000 São Paulo, SP, Brazil.
authors.forename: Érika G
authors.initials: ÉG
authors.lastname: Pinto
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270 Diadema, SP, Brazil.
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972-270 Diadema, SP, Brazil. Electronic address: psartorelli@unifesp.br.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sartorelli
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D037821:Casearia / Q000737:chemistry*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018314:Leishmania infantum / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D018515:Plant Leaves / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000977:Antiparasitic Agents; D045785:Diterpenes, Clerodane
keywords: Casearia sylvestris; Casearins; Clerodane diterpenes; Leishmania; Salicaceae; Trypanosoma cruzi