Biomaterial Database

Comparative inhibition of human cytochromes P450 1A1 and 1A2 by flavonoids. 1998

S Zhai, and R Dai, and F K Friedman, and R E Vestal

Clinical Pharmacology and Gerontology Research Unit, Department of Veterans Affairs Medical Center and Mountain States Medical Research Institute, Boise, ID 83702, USA.

Flavonoids are a class of dietary phytochemicals that modulate various biological activities. The effects of flavone and five hydroxylated derivatives on the methoxyresorufin O-demethylase activity catalyzed by cDNA-expressed human cytochromes P450 (CYP)1A1 and 1A2 were examined. Flavone was a less potent inhibitor of CYP1A1 (IC50 = 0.14 microM) than CYP1A2 (IC50 = 0.066 microM). Four hydroxylated flavone derivatives (3-hydroxy-, 5-hydroxy-, 7-hydroxy-, and 3,7-dihydroxyflavone) were also potent inhibitors of CYP1A1 (IC50 < 0.1 microM) and CYP1A2 (IC50 < 0.3 microM). For CYP1A1, 7-hydroxyflavone exhibited a competitive mode of inhibition, with a Ki value of 0.015 microM and 6-fold selectivity for CYP1A1 over CYP1A2. 3,5,7-Trihydroxyflavone (galangin) showed the highest potency toward CYP1A2. The inhibition by galangin of the methoxyresorufin O-demethylase activity of CYP1A2 was mixed-type, with a Ki value of 0.008 microM. Galangin showed 5-fold selectivity in its inhibition of CYP1A2 over CYP1A1. The results indicate that some flavonoids have high potencies and selectivities for inhibition of CYP1A isozymes. This may have important implications for cancer prevention, as well as other pharmacological and toxicological effects of these compounds.

UI	MeSH Term	Description	Entries
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D005419	Flavonoids	A group of phenyl benzopyrans named for having structures like FLAVONES.	2-Phenyl-Benzopyran,2-Phenyl-Chromene,Bioflavonoid,Bioflavonoids,Flavonoid,2-Phenyl-Benzopyrans,2-Phenyl-Chromenes,2 Phenyl Benzopyran,2 Phenyl Benzopyrans,2 Phenyl Chromene,2 Phenyl Chromenes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D019363	Cytochrome P-450 CYP1A1	A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.	CYP1A1,EROD,Ethoxyresorufin O-Deethylase,7-Ethoxyresorufin O-Deethylase,CYP 1A1,CYP1A1 Protein,Cytochrome P450 IA1,Ethoxyresorufin Dealkylase,Ethylresorufin O-Deethylase,Cytochrome P 450 CYP1A1
D065609	Cytochrome P-450 CYP1A2 Inhibitors	Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP1A2.	CYP1A2 Inhibitors,P450 CYP1A2 Inhibitors,CYP1A2 Inhibitors, P450,Cytochrome P 450 CYP1A2 Inhibitors,Inhibitors, CYP1A2,Inhibitors, P450 CYP1A2