RESUMEN
As constituents of Averrhoa bilimbi leaves we identified three new compounds (1-3) together with 12 known ones (4-15); their inhibitory activities on cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) were examined. Among the isolated compounds, the mixture of 1 and 2, and compounds 4 and 9 showed strong inhibition on CYP3A4, but mild or no inhibition on CYP2D6. These compounds revealed the characteristics of 1) time- and concentration-dependent inhibition, 2) requirement of NADPH for the inhibition, 3) no protection by nucleophiles, and 4) suppression of the inhibition by competitive inhibitor. Thus, they are suggested to be mechanism-based inactivators of CYP3A4 and CYP2D6. The kinetic parameters for the inactivation (k(inact) and K(I)) were 0.19 min(-1) and 36.7 µM for the mixture of 1 and 2, 0.126 min(-1) and 10.5 µM for 4, and 0.29 min(-1) and 23.4 µM for 9.
Asunto(s)
Averrhoa/química , Inhibidores del Citocromo P-450 CYP2D6/aislamiento & purificación , Inhibidores del Citocromo P-450 CYP3A/aislamiento & purificación , Interacciones de Hierba-Droga , Plantas Medicinales/químicaRESUMEN
From the aqueous extract of the wood of Taxus yunnanensis, which showed cytochrome P450 3A4 (CYP3A4) inhibition, a new isoflavan [(3S,4R)-4'-hydroxy-6,3'-dimethoxyisoflavan-4-ol (1)], a new degraded lignan [2,3-bis(hydroxymethyl)-7-hydroxy-6-methoxy-1-tetralone (2)], and a new lignan [(7R)-7-hydroxytaxiresinol (3)] were isolated, together with nine known lignans. Among the isolates obtained, α-conidendrin (12) showed strong CYP3A4 inhibition with an IC(50) value of 0.2 µM.