Inhibition of ethoxy- and pentoxy-resorufin dealkylases of rat liver by flavones and flavonols: structure-activity relationship

Eur J Drug Metab Pharmacokinet. Jul-Sep 1989;14(3):235-9. doi: 10.1007/BF03190104.

Abstract

The inhibitory effects of 17 flavones and flavonols on ethoxy- and pentoxy-resorufin dealkylases of rat liver were investigated. Several findings concerning the relationship between structure and activity can be pointed out. The presence or lack of hydroxyl groups on the flavane nucleus has no influence on the efficiency of inhibition. Flavone and quercetin result in the same degree of inhibition. For polyhydroxylated moleculse, the position of hydroxyl groups on A and B rings was an important factor. The more powerful inhibitors were the flavones having hydroxyl groups only on the A ring (e.g. chrysin) and the inhibitory effect was decreased by addition of hydroxyl substituents on the B group (e.g. quercetin). EROD activities were more responsive than PROD activities. Flavone and quercetin were competitive inhibitors of EROD activity whereas chrysin and morin were mixed type inhibitors. In the case of PROD activity, all four flavones were of the mixed type inhibitors.

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2B1
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytochromes / metabolism
  • Flavonoids / pharmacology*
  • Flavonols
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Oxidoreductases / antagonists & inhibitors*
  • Phenobarbital / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochromes
  • Flavonoids
  • Flavonols
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • Cyp1a2 protein, rat
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2B1
  • Phenobarbital