In vitro and in vivo activity of lignan lactones derivatives against Trypanosoma cruzi.
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.
Saraiva
Juliana
J
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
Vega
Celeste
C
Rolon
Mirian
M
da Silva
Rosangela
R
E Silva
Márcio Luis Andrade
ML
Donate
Paulo Marcos
PM
Bastos
Jairo Kenupp
JK
Gomez-Barrio
Alícia
A
de Albuquerque
Sérgio
S
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*
D007783:Lactones; D017705:Lignans