Oxidation of 3’-methoxyflavone, 4’-methoxyflavone, and 3’,4’-dimethoxyflavone and their derivatives having 5,7-dihydroxyl moieties by human cytochromes P450 1B1 and 2A13

Authors:
Publisher website
Google Scholar
Abstract
1. Oxidation of 3´-methoxyflavone, 4´-methoxyflavone, and 3´,4´-dimethoxyflavone and their derivatives containing 5,7-dihydroxyl groups by human cytochrome P450 (P450 or CYP) 1B1 and 2A13 was determined using LC-MS/MS systems. 2. 3´-Methoxyflavone and 4´-methoxyflavone were mainly O-demethylated to form 3´-hydroxyflavone and 4´-hydroxyflavone, respectively, and then 3´,4´-dihydroxyflavone at higher rates with CYP1B1 than with CYP2A13. 4´-Methoxy-5,7-dihydroxyflavone (acacetin) was found to be demethylated by CYP1B1 and 2A13 to form 4´,5,7-trihydroxyflavone (apigenin) at rates of 0.098−1 and 0.42 min−1, respectively. 3´-Methoxy-5,7-dihydroxyflavone was also demethylated by both P450s, with CYP2A13 being more active. 3. 3´,4´-Dimethoxyflavone was a good substrate for CYP1B1 but not for CYP2A13 and was found to be mainly O-demethylated to form 3´,4´-dihydroxyflavone (at a rate of 4.2 min−1) and also several ring-oxygenated products having m/z 299 fragments. Molecular docking analysis supported the proper orientation for formation of these products by CYP1B1. 4. Our present results showed that 3´- and 4´-methoxyflavone can be oxidized to their O-demethylated products and, to a lesser extent, to ring oxidation products by both P450s 1B1 and 2A13 and that 3´,4´-dimethoxyflavone is a good substrate for CYP1B1 in forming both O-demethylated and ring-oxidation products. Introduction of a 57diOHF moiety into these methoxylated flavonoids caused decreased in oxidation by CYP1B1 and 2A13.
Funding Information
  • JSPS (0, 6, 5, 0)
  • National Research Foundation of Korea
  • National Institutes of Health

This publication has 45 references indexed in Scilit: