Comparative α-Naphthoflavone and β-Naphthoflavone Inhibits the Formation of a Carcinogenic Estrogen Metabolite
| Autor: | Xin Meng, Zhigang Wang, Hui Sun, Shujun Xu, Yuan Tian, Lianrong Yang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class Metabolite CYP1B1 Bioengineering Mixed inhibition Pharmacology Biology Biochemistry Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery medicine Carcinogen Cytochrome P450 In vitro body regions 030104 developmental biology chemistry Estrogen 030220 oncology & carcinogenesis biology.protein Molecular Medicine Uncompetitive inhibitor |
| Zdroj: | International Journal of Peptide Research and Therapeutics. 23:291-295 |
| ISSN: | 1573-3904 1573-3149 |
| DOI: | 10.1007/s10989-016-9560-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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