title: Trypanocidal and leishmanicidal activities of flavonoids isolated from Stevia satureiifolia var. satureiifolia.
abstract: Context Chagas' disease and leishmaniasis produce significant disability and mortality with great social and economic impact. The genus Stevia (Asteraceae) is a potential source of antiprotozoal compounds. Objective Aerial parts of four Stevia species were screened on Trypanosoma cruzi. Stevia satureiifolia (Lam.) Sch. Bip. var. satureiifolia (Asteraceae) dichloromethane extract was selected for a bioassay-guided fractionation in order to isolate its active compounds. Additionally, the antileishmanial activity and the cytotoxicity of these compounds on mammalian cells were assessed. Materials and methods The dichloromethane extract was fractionated by column chromatography. The isolated compounds were evaluated using concentrations of 0-100 μg/mL on T. cruzi epimastigotes and on Leishmania braziliensis promastigotes for 72 h, on trypomastigotes and amastigotes of T. cruzi for 24 h and 120 h, respectively. The compounds' cytotoxicity (12.5-500 μg/mL) was assessed on Vero cells by the MTT assay. The structure elucidation of each compound was performed by spectroscopic methods and HPLC analysis. Results The dichloromethane extracts of Stevia species showed significant activity on T. cruzi epimastigotes. The flavonoids eupatorin (1.3%), cirsimaritin (1.9%) and 5-desmethylsinensetin (1.5%) were isolated from S. satureiifolia var. satureiifolia extract. Eupatorin and 5-desmethylsinensetin showed IC50 values of 0.2 and 0.4 μg/mL on T. cruzi epimastigotes and 61.8 and 75.1 μg/mL on trypomastigotes, respectively. The flavonoid 5-desmethylsinensetin showed moderate activity against T. cruzi amastigotes (IC50  value = 78.7 μg/mL) and was the most active compound on L. braziliensis promastigotes (IC50  value = 37.0 μg/mL). Neither of the flavonoids showed cytotoxicity on Vero cells, up to a concentration of 500 μg/mL.
authors.affiliation: a Instituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Facultad de Farmacia y Bioquímica , Universidad de Buenos Aires , Buenos Aires , Argentina ;|b Instituto de Tecnología Química (INTEQUI-CONICET) , Universidad Nacional de San Luis , San Luis , Argentina ;
authors.forename: María Florencia
authors.initials: MF
authors.lastname: Beer
authors.affiliation: c Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU) (UBA-CONICET) , Facultad de Farmacia y Bioquímica , Buenos Aires , Argentina ;|d Instituto de Microbiología y Parasitología Médica (IMPaM) (UBA-CONICET) , Facultad de Medicina , Buenos Aires , Argentina ;
authors.forename: Fernanda Maria
authors.initials: FM
authors.lastname: Frank
authors.affiliation: a Instituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Facultad de Farmacia y Bioquímica , Universidad de Buenos Aires , Buenos Aires , Argentina ;|c Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU) (UBA-CONICET) , Facultad de Farmacia y Bioquímica , Buenos Aires , Argentina ;
authors.forename: Orlando
authors.initials: O
authors.lastname: Germán Elso
authors.affiliation: c Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU) (UBA-CONICET) , Facultad de Farmacia y Bioquímica , Buenos Aires , Argentina ;|d Instituto de Microbiología y Parasitología Médica (IMPaM) (UBA-CONICET) , Facultad de Medicina , Buenos Aires , Argentina ;
authors.forename: Augusto
authors.initials: A
authors.lastname: Ernesto Bivona
authors.affiliation: c Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU) (UBA-CONICET) , Facultad de Farmacia y Bioquímica , Buenos Aires , Argentina ;|d Instituto de Microbiología y Parasitología Médica (IMPaM) (UBA-CONICET) , Facultad de Medicina , Buenos Aires , Argentina ;
authors.forename: Natacha
authors.initials: N
authors.lastname: Cerny
authors.affiliation: a Instituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Facultad de Farmacia y Bioquímica , Universidad de Buenos Aires , Buenos Aires , Argentina ;
authors.forename: Gustavo
authors.initials: G
authors.lastname: Giberti
authors.affiliation: c Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU) (UBA-CONICET) , Facultad de Farmacia y Bioquímica , Buenos Aires , Argentina ;|d Instituto de Microbiología y Parasitología Médica (IMPaM) (UBA-CONICET) , Facultad de Medicina , Buenos Aires , Argentina ;
authors.forename: Emilio
authors.initials: E
authors.lastname: Luis Malchiodi
authors.affiliation: a Instituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Facultad de Farmacia y Bioquímica , Universidad de Buenos Aires , Buenos Aires , Argentina ;|e Cátedra de Farmacognosia, Facultad de Farmacia y Bioquímica , Universidad de Buenos Aires , Buenos Aires , Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Susana Martino
authors.affiliation: a Instituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Facultad de Farmacia y Bioquímica , Universidad de Buenos Aires , Buenos Aires , Argentina ;
authors.forename: María Rosario
authors.initials: MR
authors.lastname: Alonso
authors.affiliation: a Instituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Facultad de Farmacia y Bioquímica , Universidad de Buenos Aires , Buenos Aires , Argentina ;|e Cátedra de Farmacognosia, Facultad de Farmacia y Bioquímica , Universidad de Buenos Aires , Buenos Aires , Argentina.
authors.forename: Valeria
authors.initials: V
authors.lastname: Patricia Sülsen
authors.affiliation: c Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU) (UBA-CONICET) , Facultad de Farmacia y Bioquímica , Buenos Aires , Argentina ;|d Instituto de Microbiología y Parasitología Médica (IMPaM) (UBA-CONICET) , Facultad de Medicina , Buenos Aires , Argentina ;
authors.forename: Silvia Ines
authors.initials: SI
authors.lastname: Cazorla
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005591:Chemical Fractionation; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000254:growth & development; D008752:Methylene Chloride / Q000737:chemistry; D021261:Parasitic Sensitivity Tests; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal; D012997:Solvents / Q000737:chemistry; D036625:Stevia / Q000737:chemistry; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development; D014709:Vero Cells
chemical_list: D010936:Plant Extracts; D012997:Solvents; D014344:Trypanocidal Agents; D008752:Methylene Chloride
keywords: Leishmania braziliensis; phenolic compounds; Stevia spp.; Trypanosoma cruzi