TABLE 1
Structure of the flavonols and flavones and their mean Ki values (micromolar) as inhibitors of diclofenac 4′-hydroxylase activity in the CYP2C9 RECO system
Incubations performed using 0.3 pmol of RECO CYP2C9, 2.5 to 100 μM diclofenac, and a test compound with a concentration in the range 0 to approximately 6 times Ki. 4′-Hydroxydiclofenac/diclofenac was <1/20 in all assays. Global standard error for data fitting was less than 30% and γ2 > 0.90 for each effector.
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| Flavonols | K i | Flavones | K i | |||
| Galangin: 5,7=OH | 0.15 | Flavone | 17 | |||
| Fisetin: 7,3′,4′=OH | 1.7 | 7-Hydroxyflavone: 7=OH | 2.0 | |||
| Kaempferol: 5,7,4′=OH | 1.1 | 6-Hydroxyflavone: 6=OH | 2.2a | |||
| Morin: 5,7,2′,4′=OH | 1.8 | Chrysin: 5,7=OH | 1.0 | |||
| Quercetin: 5,7,3′,4′=OH | 2.0 | Baicalein: 5,6,7=OH | 0.91 | |||
| Apigenin: 5,7,4′=OH | 2.0 | |||||
| Luteolin: 5,7,3′,4′=OH | 1.3 | |||||
| Scutellarein: 5,6,7,4′=OH | 1.7 | |||||
| Wogonin: 5,7 = OH, 8=OCH3 | 1.0 | |||||
| Scutellarin (scutellarein 7-O-β-d-glucuronide) | 75 | |||||
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| Baicalin (baicalein 7-O-β-d-glucuronide) | 40 | |||
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↵ a Noncompetitive inhibitor; all others are competitive inhibitors.