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Interaction of Isoflavonoids With Human Liver Microsomal Cytochromes P450: Inhibition of CYP Enzyme Activities

Interaction of Isoflavonoids With Human Liver Microsomal Cytochromes P450: Inhibition of CYP Enzyme Activities

Michaela Kopečná-Zapletalová, Kristýna Krasulová, Pavel Anzenbacher, Petr Hodek, Eva Anzenbacherová

Xenobiotica. 2017 Apr;47(4):324-331.

PMID: 27312150

Abstract:

1. The possibility of interaction of isoflavonoids with concomitantly taken drugs to determined isoflavonoids safety was studied. Inhibition of nine forms of cytochrome P450 (CYP3A4, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6 and CYP2E1) by 12 isoflavonoids (daidzein, genistein, biochanin A, formononetin, glycitein, equol and six glucosides, daidzin, puerarin, genistin, sissotrin, ononin and glycitin) was studied systematically. 2. The most potent inhibitors were genistein and daidzein inhibiting noncompetitively the CYP2C9 with Ki of 35.95 ± 6.96 and 60.56 ± 3.53 μmol/l and CYP3A4 (inhibited by genistein with Ki of 23.25 ± 5.85 μmol/l also by a noncompetitive mechanism). Potent inhibition of CYP3A4 was observed also with biochanin A (Ki of 57.69 ± 2.36 μmol/l) and equol (Ki of 38.47 ± 2.32 μmol/l). 3. Genistein and daidzein inhibit noncompetitively CYP3A4 and CYP2C9. With plasma levels in micromolar range, a clinically important interaction with concomitantly taken drugs does not seem to be probable.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP5928267	Sissotrin		5928-26-7	Price

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