Aromatase inhibition by flavonoids

J Steroid Biochem Mol Biol. 1990 Oct;37(2):257-60. doi: 10.1016/0960-0760(90)90335-i.

Abstract

Several synthetic flavones were found to inhibit the aromatization of androstenedione to estrone catalyzed by human placental microsomes. Twenty-one compounds were tested and the IC50 of the most active were: flavone, 10 microM; 7-hydroxyflavone, 0.5 microM; 7,4'-dihydroxyflavone, 2.0 microM; flavanone, 8.0 microM; and 4'-hydroxyflavanone, 10 microM. Most of the others had IC50 values ranging from 80 to greater than 200 microM. These findings show that 4'-hydroxylation results in either no change or very little change in IC50 for flavanone, isoflavone and isoflavanone as well as other ring A hydroxylated flavones. Derivatives of flavone with a hydroxyl substituent at position 5, 6 and 7 were also screened. 7-Hydroxyflavone (11) was the most effective competitive inhibitor (IC50 = 0.5 microM) with an apparent Ki value of 0.25 microM. Compound 11 also induced a change in the absorption spectrum of the aromatase cytochrome P-450 which is indicative of substrate displacement. The relative binding affinities of the flavonoid analogs were determined and only ring A adn ring B dihydroxylated analogs were found to bind to the estrogen receptor.

MeSH terms

  • Animals
  • Aromatase Inhibitors*
  • Female
  • Flavonoids / metabolism
  • Flavonoids / pharmacology*
  • Humans
  • Kinetics
  • Microsomes / enzymology
  • Molecular Structure
  • Placenta / enzymology*
  • Pregnancy
  • Rats
  • Receptors, Estrogen / metabolism
  • Structure-Activity Relationship
  • Uterus / metabolism

Substances

  • Aromatase Inhibitors
  • Flavonoids
  • Receptors, Estrogen