title: In vitro and in vivo activity of lignan lactones derivatives against Trypanosoma cruzi.
abstract: The trypanocidal effect of six lignan lactones, (-)-cubebin (1), (-)-O-methyl cubebin (2), (-)-O-benzyl cubebin (3), (-)-6,6'-dinitrohinokinin (4), (-)-hinokinin (5) and dimethoxymorelensin (6), previously synthesized by our research group, was evaluated in vitro and in vivo. The compounds with higher anti-epimastigote activity were screened against intracellular amastigote of Trypanosoma cruzi. Among these, compound 5 was selected to be assayed in vivo. It was observed that compounds 5, 6 and 2 showed higher trypanocidal activity against epimastigote forms of T. cruzi, displaying inhibitory concentration (IC(50)) values of 0.67, 3.89 and 31.35 muM, respectively. These compounds were also evaluated against intracellular amastigote forms of T. cruzi, with five displaying similar activity to benznidazole. In vivo assays showed significant reduction of parasitaemia after administration of five in mice infected.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Avenida do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil. jus@fcfrp.usp.br
authors.forename: Juliana
authors.initials: J
authors.lastname: Saraiva
authors.forename: Celeste
authors.initials: C
authors.lastname: Vega
authors.forename: Mirian
authors.initials: M
authors.lastname: Rolon
authors.forename: Rosangela
authors.initials: R
authors.lastname: da Silva
authors.forename: Márcio Luis Andrade
authors.initials: ML
authors.lastname: E Silva
authors.forename: Paulo Marcos
authors.initials: PM
authors.lastname: Donate
authors.forename: Jairo Kenupp
authors.initials: JK
authors.lastname: Bastos
authors.forename: Alícia
authors.initials: A
authors.lastname: Gomez-Barrio
authors.forename: Sérgio
authors.initials: S
authors.lastname: de Albuquerque
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D017705:Lignans / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D007783:Lactones; D017705:Lignans