17β-Estradiol (E2) is hydrolyzed to 2-hydroxy-E2 and 4-hydroxy-E2 (4-OH-E2) via cytochrome P450 (CYP) 1B1. In estrogen target tissues including the mammary gland, ovaries and uterus, CYP1B1 is highly expressed, and 4-OH-E2 is predominantly formed in cancerous tissues. In the present study, we investigated the inhibitory activity of α-naphthoflavone and β-naphthoflavone against CYP1B1 using estrogen E2 as substrate in vitro to reveal structure–activity relationship between structure of flavonoids and inhibition. The results showed that α-naphthoflavone and β-naphthoflavone possessed inhibitory activity against CYP1B1-mediated E2 and the inhibition of α-naphthoflavone was stronger than β-naphthoflavone. By kinetic analyses, α-naphthoflavone displayed uncompetitive inhibition, while β-naphthoflavone displayed mixed inhibition. Taken together, the data suggested that the benzo at A ring of flavonoids play a prominent role in CYP1B1 inhibition, especially 7,8-benzo is better than 5,6-benzo. This study may help to reveal the relationship between the structure of flavonoids and the inhibition CYP1B1 for discovering new drugs in cancer therapy and prevention.
International Journal of Peptide Research and Therapeutics – Springer Journals
Published: Oct 14, 2016
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