Methoxyresorufin O-demethylation

Flavonoids, especially flavones and flavonols, also directly bind to several CYP isoforms (lAl, 1A2, IBl, 3A4) involved in xenobiotics metabolism and inhibit enzyme activity. Structure-activity relationships show rather high isoform selectivities depending on the flavonoid substitution pattern and contrasted inhibition mechanisms. For instance, inhibition by flavonoids of 7-methoxyresorufin O-demethylation in microsomes enriched in CYP lAl and 1A2 reveals that galangin (3,5,7-trihydroxyflavone) is a mixed inhibitor of CYP 1A2 (.ST = 8 nM) and a five times less potent inhibitor of CYP 1A1. By contrast, 7-hydroxy flavone is a competitive inhibitor of CYP lAl (Aii = 15 nM) and a six times less potent inhibitor of CYP 1A2. In addition, fairly selective inhibition of CYP IBl (specifically detected in cancer cells) by some flavonoids has been reported. For example, 5,7-dihydroxy-4 -methoxyflavone inhibits IBl, 1 Al, and 1A2 with IC50 values of 7, 80, and 80 nM, respectively. ... 

Kim D, Guengerich FP. Enhancement of 7-methoxyresorufin O-demethylation activity of human cytochrome P450 1A2 by molecular breeding. Arch Biochem Biophys 2004 432 102-8. 

---