a-Naphthoflavone-5,6-oxide | 77413-93-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: a-Naphthoflavone-5,6-oxide
• 英文别名: 1a,9b-Dihydro-4-phenyl-2H-oxireno(3,4)naphtho(1,2-b)pyran-2-one；8-phenyl-3,9-dioxatetracyclo[9.4.0.02,4.05,10]pentadeca-1(15),5(10),7,11,13-pentaen-6-one
• CAS: 77413-93-5
• 化学式: C₁₉H₁₂O₃
• 分子量: 288.302
• InChiKey: RVESQEDXDIARBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  α-萘黄酮 在 human liver microsome 、 NADPH-generating system 作用下， 以 phosphate buffer 为溶剂， 反应 0.33h， 生成 a-Naphthoflavone-5,6-oxide
  参考文献：
  名称：

  Involvement of P4503A in the metabolism of 7,8-benzoflavone by human liver microsomes

  摘要：

  1. The metabolism of 7,8-benzoflavone (ANF) was studied in human liver microsomal fractions. Five metabolites were generated and tentatively identified as ANF 5,6-oxide, 5,6-dihydrodiol, 7,8-dihydrodiol, 6-hydroxy ANF, and 7-hydroxy ANF based on UV and mass spectral analysis.2. The involvement of P4503A in the metabolism of ANF was confirmed by the following observations: (1) correlation of ANF 5,6-oxide formation was noted with testosterone 6 beta-hydroxylation, an indicator of P4503A, in human liver microsomal fractions; (2) metabolism of ANF was inhibited by various selective P4503A enzyme inhibitors; (3) rabbit antibody raised against P4503A4 inhibited the ANF metabolism by > 80%; and (4) microsomal fractions that specifically expressed P4503A4 metabolized ANF to oxidized metabolites.3. These results indicate that P4503A isoform(s) mainly metabolize ANF to oxidized derivatives in human liver microsomal fractions.

  DOI：

  10.3109/00498259409038665

文献信息

• Cytochrome P450 3A activities and their modulation by α-naphthoflavone in vitro are dictated by the efficiencies of model experimental systems
  作者：Lucie Bořek-Dohalská、Marie Stiborová

  DOI：10.1135/cccc2009525

  日期：——

  The knowledge on efficiencies of differentin vitrosystems containing cytochromes P450 (CYP) of a 3A subfamily is crucial to screen potential substrates of these CYPs. We evaluated and compared efficiencies of severalin vitroCYP3A enzymatic systems to oxidize the model substrates, α-NF and testosterone, under the standardized experimental conditions. Five CYP3A systems were tested: (i) human hepatic microsomes rich in CYP3A4, (ii) hepatic microsomes of rabbits treated with a CYP3A6 inducer, rifampicine, (iii) microsomes of Baculovirus transfected insect cells containing recombinant human CYP3A4 and NADPH:CYP reductase with or without cytochrome b₅(Supersomes^TM), (iv) membranes isolated fromEscherichia coli, containing recombinant human CYP3A4, NADPH:CYP reductase and cytochrome b₅, and (v) human CYP3A4 or rabbit CYP3A6 reconstituted with NADPH:CYP reductase with or without cytochrome b₅in liposomes. All systems oxidize testosterone to its 6β-hydroxylated metabolite and α-NF to trans-7,8-dihydrodiol and 5,6-epoxide. The most efficient systems oxidizing both compounds were CYP3A4-Supersomes^TMcontaining cytochrome b₅, followed by human hepatic microsomes. This finding suggests these systems to be suitable for general evaluating a variety of compounds as potential substrates of CYP3A4. The lowest efficiencies to oxidize α-NF and testosterone were found for CYP3A4 expressed in membranes ofE. coli, and for reconstituted CYP3A4 or CYP3A6. Utilizing the tested enzymatic systems, we also explain here the discrepancies, which showed previously the controversial effects of α-NF on CYP3A-mediated reactions. We demonstrate that inhibition or stimulation of the CYP3A-mediated testosterone hydroxylation by α-NF is dictated by efficiencies of individual enzymatic systems to oxidize the CYP3A substrates.

  不同in vitro系统中含有3A亚家族细胞色素P450（CYP）的效率知识对筛选这些CYP的潜在底物至关重要。我们评估并比较了几个in vitro CYP3A酶系统在标准化实验条件下氧化模型底物α-NF和睾酮的效率。共测试了五个CYP3A系统：（i）富含CYP3A4的人类肝微粒体，（ii）经CYP3A6诱导剂利福平处理的兔肝微粒体，（iii）含有重组人类CYP3A4和NADPH：CYP还原酶以及有或无细胞色素b₅的杆状病毒转染昆虫细胞微粒体（Supersomes^TM），（iv）含有重组人类CYP3A4、NADPH：CYP还原酶和细胞色素b₅的大肠杆菌膜分离物，以及（v）人类CYP3A4或兔CYP3A6与NADPH：CYP还原酶及有或无细胞色素b₅在脂质体中重组。所有系统均将睾酮氧化为其6β-羟基化代谢物，将α-NF氧化为反式-7,8-二氢二醇和5,6-环氧化物。氧化这两种化合物效率最高的系统是含有细胞色素b₅的CYP3A4-Supersomes^TM，其次是人类肝微粒体。这一发现表明这些系统适用于一般评估各种化合物作为CYP3A4潜在底物。氧化α-NF和睾酮的效率最低的是在大肠杆菌膜中表达的CYP3A4以及重组的CYP3A4或CYP3A6。利用测试的酶系统，我们还在此解释了先前显示的α-NF对CYP3A介导的反应具有争议性效果的差异。我们证明，α-NF对CYP3A介导的睾酮羟化的抑制或刺激取决于各个酶系统氧化CYP3A底物的效率。
• Involvement of P4503A in the metabolism of 7,8-benzoflavone by human liver microsomes
  作者：H. S. Lee、C. B. Jin、H. S. Chong、C. H. Yun、J. S. Park、D. H. Kim

  DOI：10.3109/00498259409038665

  日期：1994.1

  1. The metabolism of 7,8-benzoflavone (ANF) was studied in human liver microsomal fractions. Five metabolites were generated and tentatively identified as ANF 5,6-oxide, 5,6-dihydrodiol, 7,8-dihydrodiol, 6-hydroxy ANF, and 7-hydroxy ANF based on UV and mass spectral analysis.2. The involvement of P4503A in the metabolism of ANF was confirmed by the following observations: (1) correlation of ANF 5,6-oxide formation was noted with testosterone 6 beta-hydroxylation, an indicator of P4503A, in human liver microsomal fractions; (2) metabolism of ANF was inhibited by various selective P4503A enzyme inhibitors; (3) rabbit antibody raised against P4503A4 inhibited the ANF metabolism by > 80%; and (4) microsomal fractions that specifically expressed P4503A4 metabolized ANF to oxidized metabolites.3. These results indicate that P4503A isoform(s) mainly metabolize ANF to oxidized derivatives in human liver microsomal fractions.