Tonantzitlolones from Stillingia lineata ssp lineata as potential inhibitors of chikungunya virus

作者:Techer S; Girard Valenciennes E; Retailleau P; Neyts J; Gueritte F; Leyssen P; Litaudon M; Smadja J; Grondin I*
来源:Phytochemistry Letters, 2015, 12: 313-319.
DOI:10.1016/j.phytol.2015.04.023

摘要

With the purpose of discovering new chemical classes of molecules, in particular those with selective antiviral activity, extracts from plants growing in Reunion Island were systematically evaluated in a chikungunya virus-cell-based assay. The entire ethyl acetate extract obtained from the stem bark of Stillingia lineata ssp. lineata (Euphorbiaceae) exhibited selective antiviral activity against the chikungunya virus with an EC50 < 0.8 mu g/mL, whereas only a weak cytotoxic effect was observed on the host cells. A phytochemical investigation of this extract led to the isolation of tonantzitlolone A and tonantzitlolone B (1 and 2), together with the new 4'-hydroxytonantzitlolone, named tonantzitlolone C (3), which has an uncommon C15-flexibilane skeleton, as well as in the new ent-12 alpha-hydroxy-3,7-dioxoisopimara-8,15-diene (4). Subsequent evaluation for inhibition of chikungunya virus replication in cellulo demonstrated that the 4'-acetoxytonantzitlolone (2) was endowed with antiviral activity against CHIKV.