Sear~h for Inhibitors of Cytchronxe P450 3A4 froiyi foods

搜索 Cytchronxe P450 3A4 Froiyi 食品抑制剂

• 批准号: 14571999
• 负责人: TSUKAMOTO Sachiko
• 金额: $ 2.18万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571999/
• 关键词: cytochrome P450; drug metabolism; food; grapefruit juice; white pepper; strawberry

Cytochrome P450(CYP)enzymes are home-containing monooxygenases and constitute three families, CYP1, CYP2, and CYP3.These enzymes have been mainly expressed in liver microsomes, and are recognized to be responsible for drug metabolism, carcinogenesis, and degradation of xenobiotics. CYPs are also responsible for the biosynthesis of lipids, steroids, and other secondary metabolites.CYP3A4 is the most abundant enzyme in human liver microsomes ; approximately 30% of the total CYP was suggested to be CYP3A4.Recent investigations have shown that more than 50% of clinically used drugs are oxidized by CYP3A4.It is reported that concomitant oral administration of several foods and herbs affect drug metabolism in humans by inhibiting CYP3A4 activity and that grapefruit juice alters the pharmacokinetics of various drugs, including cyclosporine, midazolam, dihydropyridine-type calcium channel blockers, and triazolam.In the course of our study of.CYP inhibitors, we have reported the isolation and structure elucidation of furanocoumarins, paradisins A, B, and C, from grapefruit juice, bisalkaloids, dipiperamides A-E, from the white pepper Piper nigrum, and three glycosides from the strawberry Fragaria ananassa Duch.cv.Tochiotome.

细胞色素P450(CYP)酶是一类单加氧酶，由CYP1、CYP2和CYP3三个家族组成。这些酶主要在肝微粒体中表达，被认为与药物代谢、致癌和外源物质降解有关。 CYP 还负责脂质、类固醇和其他次级代谢产物的生物合成。CYP3A4 是人肝微粒体中最丰富的酶； CYP3A4 约占总 CYP 的 30%。最近的研究表明，超过 50% 的临床使用药物被 CYP3A4 氧化。据报道，同时口服几种食物和草药会通过抑制CYP3A4 活性以及葡萄柚汁改变多种药物的药代动力学，包括环孢素、咪达唑仑、二氢吡啶型药物在我们研究 CYP 抑制剂的过程中，我们报道了从葡萄柚汁中分离出呋喃香豆素、paradisins A、B 和 C、从白胡椒中分离出的双生物碱、双哌酰胺 A-E 以及结构解析黑胡椒和来自草莓 Fragaria ananassa Duch.cv.Tochiotome 的三种苷。

项目成果

Sachiko Tsukamoto: "CYP3A4 Inhibitory Activity of New Bisalkaloids Dipiperamides D and E and Cognate Alkaloids from the White Pepper"Bioorg. Med. Chem.. 10(9). 2981-2985 (2002)

Sachiko Tsukamoto：“新型双生物碱 Dipiperamides D 和 E 以及来自白胡椒的同源生物碱的 CYP3A4 抑制活性”Bioorg。

Sachiko Tsukamoto: "CYP3A4 Inhibitory Activity of New Bisalkaloids Dipiperamides D and E and Cognate Alkaloids from the White Pepper"Bioorg.Med.Chem.. 10(9). 2981-2985 (2002)

Sachiko Tsukamoto：“新型双生物碱 Dipiperamides D 和 E 以及来自白胡椒的同源生物碱的 CYP3A4 抑制活性”Bioorg.Med.Chem.. 10(9)。

Sachiko Tsukamoto: "Dipiperamides A, B, and C : bisalkaloids from the white pepper Piper nigrum inhibiting CYP3A4 activity"Tetrahedron. 58(9). 1667-1671 (2002)

Sachiko Tsukamoto：“双哌酰胺 A、B 和 C：来自白胡椒胡椒的双生物碱抑制 CYP3A4 活性”四面体。

Tomihisa Ohta: "Localization and contents of paradisins, the most potent CYP3A4 inhibitors, in a grapefruit Citrus paradisii and grapefruit juice"Nat. Med. 56(6). 264-267 (2002)

Tomihisa Ohta：“葡萄柚 Citrus paradisii 和葡萄柚汁中 Paradisins（最有效的 CYP3A4 抑制剂）的定位和含量”Nat。

Tomihisa Ohta: "Dihydroxybergamottin Caproate as a Potent and Stable CYP3A4 Inhibitor."Bioorg.Med.Chem.. 10. 969-973 (2002)

Tomihisa Ohta：“二羟基佛手柑己酸酯作为有效且稳定的 CYP3A4 抑制剂。”Bioorg.Med.Chem.. 10. 969-973 (2002)