Inhibition of CYP450 enzymes by quassinoids from Picrasma quassioides leaves

Abstract Three new C 20 quassinoids, namely, nigakilactones R (1), S ( 2 ), and T ( 3 ), along with 13 known ones, were isolated on Picrasma quassioides leaves. Their structures were elucidated by an extensive spectroscopic analysis. All the compounds were tested for their inhibitory activities against the six major CYP450 enzymes CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4. Compounds 1 , 10 , 11, and 12 showed potential as inhibitor of CYP2C19 with IC 50 values of 62.6, 160.0, 61.5, and 35.8 μM, respectively. Compounds 1 , 3, and 6 exhibited considerable inhibition against CYP3A4 with IC 50 values of 51.4, 97.2, and 62.8 μM, respectively. CYP2C19 and 3A4 are important metabolic enzymes involved in many drugs. Our study may provide a cautionary measure to avoid the combined use of CYP2C19- and 3A4-catalyzed drugs with the quassinoid-containing herbs and related formulae.