The Structure-Activity Correlation on the Inhibitory Effects of Flavonoids on Cytochrome P450 3A Activity(Biopharmacy)
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概要
- 論文の詳細を見る
Flavonoids are divided into flavones, flavonols, flavanones, and isoflavones etc. according to their basal structure, and are known to include compounds with physiological and pharmacological effects such as anti-oxidant, anti-tumor, and anti-inflammation activities. The ingestion of flavonoids may induce pharmacokinetic interactions through the co-administration of drugs. In this study, we investigated the inhibitory potentials on cytochrome P450 (CYP) 3A activity of 23 flavonoids using human liver microsomes, and tried to identify the molecular features that cause the inhibition of CYP3A. The activity of testosterone 6β-hydroxylate was evaluated to quantify CYP3A activity. We analyzed Quantification Theory I, in which extreme values of the inhibitory effects of CYP3A activity were tested with flavonoids supplied at a level of 10μM. The inhibitory effects of flavonoids ranged widely from 1.5μM to more than 100μM for the half maximal inhibitory concentration. Because the inhibitory effects were only weakly correlated with the pK_a value, the inhibitory effects could not be accounted for by the molecular characteristics of the flavonoids. On the other hand, flavones with the basal structure and hydroxylation at positions 7 and 4' showed significantly increased inhibitory effects on CYP3A activity. In addition, the hydroxylation of position 2' and 3', methoxylation of position 4', and the isoflavone basal structure significantly decreased the inhibitory effects on CYP3A activity. In conclusion, the basal structure and the substituents of flavonoids are important in the inhibitory effects of flavonoids on CYP3A activity.
- 2009-04-01
著者
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Nishiguchi Kohshi
Department of Hospital Pharmacy, School of Medicine, Kobe University
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Takara Kohji
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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Takara Kohji
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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TSUJIMOTO Masayuki
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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Nishiguchi Kohshi
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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HORIE Maya
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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HONDA Hiroko
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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Horie Maya
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Honda Hiroko
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Tsujimoto Masayuki
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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