苯并(a)芘-7,8-二醇 | 57303-99-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 中文名称: 苯并(a)芘-7,8-二醇
• 英文名称: 7,8-dihydroxybenz[a]pyrene
• 英文别名: benzo[a]pyrene-7,8-dihydrodiol；uridine 5′-diphosphoglucuronic acid；benzo(a)pyrene-7,8-diol；7,8-Dihydroxybenzo[a]pyrene；benzo[a]pyrene-7,8-diol
• CAS: 57303-99-8
• 化学式: C₂₀H₁₂O₂
• 分子量: 284.314
• InChiKey: FWKXMJCJEOUXDE-UHFFFAOYSA-N

物化性质

• 沸点：
  572.3±23.0 °C(Predicted)
• 密度：
  1.473±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

苯并[a]芘-7,8-二醇已知的人类代谢物包括(2S,3S,4S,5R)-3,4,5-三羟基-6-(8-羟基苯并[a]芘-7-基)氧杂环己烷-2-羧酸和4-氧杂六环[11.6.2.02,8.03,5.010,20.017,21]二十一烷-1(20),2(8),3(5),6,9,11,13(21),14,16,18-癸烯-6,7-二醇。

Benzo[a]pyrene-7,8-diol has known human metabolites that include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-(8-hydroxybenzo[a]pyren-7-yl)oxyoxane-2-carboxylic acid and 4-Oxahexacyclo[11.6.2.02,8.03,5.010,20.017,21]henicosa-1(20),2(8),3(5),6,9,11,13(21),14,16,18-decaene-6,7-diol.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  苯并(a)芘-7,8-二醇 生成 7,8-二羟基-9,10-环氧-7,8,9,10-四氢苯并[A]芘
  参考文献：
  名称：

  ALONSO, E., EINSTEIN QUART., 5,(1987) N 3, 90-94

  摘要：

  DOI：
• 作为产物：
  描述：

  苯并[a]芘 在 multiwalled carbon nanotube modified glassy carbon electrode 作用下， 以 aq. phosphate buffer 、 乙醇 为溶剂， 反应 0.08h， 生成 苯并(a)芘-7,8-二醇
  参考文献：
  名称：

  MWCNT修饰电极表面上苯并[ a ]的仿生氧化为醌代谢物，作为半胱氨酸氧化介质

  摘要：

  含有多个芳香族烃类化合物（PAHs）的苯并（a）py（BaP），包含几个应变的苯环，是生理系统中致癌和致突变性的代表性有机化合物。通常，细胞色素c，过氧化物酶并且某些土壤细菌将这些化合物氧化为各自的羟基化代谢物，例如BaP-7,8-二醇（BaP-2OH），它们可以与DNA，RNA和蛋白质相互作用，进而使细胞系统功能失调。这些化合物的结构-活性关系尚不清楚，因此，有必要采用一种新的分析方法来描述PAHs氧化背后的复杂机理。在本文中，我们报告了一种在生理条件下（pH 7磷酸盐缓冲溶液）在多壁碳纳米管（MWCNT）修饰的玻碳电极（GCE / MWCNT）上对BaP进行表面限制氧化的简单电化学方法。已经发现，在高正电势（相对于Ag / AgCl为1.2 V）下，MWCNT表面吸附的BaP（非电活性化合物）被电氧化为高氧化还原活性的BaP-2OH化合物，其中，水分子通过羟基自由基中间体氧化为分子氧。

  DOI：

  10.1016/j.electacta.2020.136367

文献信息

• Synthesis of 13C4-labelled oxidized metabolites of the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene
  作者：Anhui Wu、Daiwang Xu、Ding Lu、Trevor M. Penning、Ian A. Blair、Ronald G. Harvey

  DOI：10.1016/j.tet.2012.05.130

  日期：2012.9

  sensitive stable isotope dilution LC/MS method for analysis of BaP metabolites. We now report efficient syntheses of 13C4-BaP and the complete set of its 13C4-labelled oxidized metabolites needed as internal standards They include the metabolites not involved in carcinogenesis (Group A) and the metabolites implicated in initiation of cancer (Group B). The synthetic approach is novel, entailing use of Pd-catalyzed

  多环芳烃 (PAH)，例如苯并 [ a ] 芘 (B a P)，是普遍存在的环境污染物，与导致肺癌有关。B a P 是烟草烟雾的一种成分，通过酶促转化为与 DNA 相互作用的活性形式。我们之前报道了一种用于分析 B a P 代谢物的灵敏的稳定同位素稀释 LC/MS 方法的开发。我们现在报告了13 C 4 -B a P 的有效合成及其完整的13 C 4标记氧化代谢物，需要作为内标。它们包括不参与致癌作用的代谢物（A 组））和与癌症发生有关的代谢物（B组）。该合成方法是新颖的，需要使用 Pd 催化的 Suzuki、Sonogashira 和 Hartwig 交叉偶联反应与 PtCl 2催化的炔属化合物环化反应相结合。这种合成方法需要更少的步骤，使用更温和的条件，并且产物分离比传统的 PAH 合成方法更简单。13 C 4 -B a P 和13 C 4 -B a P-8-ol的合成各只需要四步，并且13
• Synthesis of the <i>o</i>-Quinones and Other Oxidized Metabolites of Polycyclic Aromatic Hydrocarbons Implicated in Carcinogenesis
  作者：Ronald G. Harvey、Qing Dai、Chongzhao Ran、Trevor M. Penning

  DOI：10.1021/jo030348n

  日期：2004.3.1

  benzo[a]pyrene (BPQ), 7,12-dimethylbenz[a]anthracene (DMBAQ), and benz[a]anthracene (BAQ), implicated as active carcinogenic metabolites of the parent polycyclic aromatic hydrocarbons (PAHs), are reported. These PAH quinones also serve as starting compounds for the synthesis of the other active metabolites of these PAHs thought to be involved in their mechanism(s) of carcinogenesis. The latter include the corresponding

  苯并[ a ] py（BPQ），7,12-二甲基苯并[ a ]蒽（DMBAQ）和苯并[ a ]蒽（BAQ）的邻苯醌衍生物的高效合成，被认为是母体的活性致癌代谢物报道了多环芳烃（PAH）。这些PAH醌也用作这些PAH的其他活性代谢产物合成的起始化合物，这些活性代谢产物被认为与它们的致癌机理有关。后者包括相应Ó -catechols，反式-dihydrodiols，以及相应的抗-和顺-二醇环氧化物。
• Modulation of Cytochrome P4501-mediated Bioactivation of Benzo[a]pyrene by Volatile Allyl Sulfides in Human Hepatoma Cells
  作者：Hyang Sook CHUN、Hyun Jung KIM、Eun Hye CHOI

  DOI：10.1271/bbb.65.2205

  日期：2001.1

  Allyl sulfides such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), typical flavor components of Allium vegetables, have been shown to inhibit benzo[a]pyrene (B[a]P)-induced carcinogenesis in animal models. As a possible mechanism of this inhibition, the effect of these volatile substances on cytochrome P450 (CYP)1 (CYP1A1, 1A2 and 1B1)-mediated bioactivation of B[a]P was investigated using a human hepatoma cell model (HepG2). DADS and DATS inhibited the B[a]P-induced ethoxyresorufin O-deethylase (EROD) activity, a marker enzyme for CYP1, by 30-90% and 70-95% at 100-1,000 μM concentration, respectively. The cell viability, an indicator of the capacity to inhibit B[a]P bioactivation, was increased by treatments of 100-1,000 μM DADS and 10-100 μM DATS. Immunoblot results indicated that the B[a]P inducible CYP1A2 protein was suppressed by 100-1,000 μM of DADS and 10-100 μM of DATS, but CYP1A1 and 1B1 were not detectable in any microsomes. Analysis of B[a]P metabolites revealed that the level of 7,8-diol formed was significantly reduced in the DADS and DATS treated microsomes as compared to the control. The level of 9,10-diol and 4,5-diol formed was also lowered by the allyl sulfide treatments. These results suggest that the protective mechanism of allyl sulfides on B[a]P-induced carcinogenesis is possibly related with the modulation of CYP1-mediated bioactivation of B[a]P.

  烯丙基硫醚，如二烯丙基硫醚（DAS）、二烯丙基二硫化物（DADS）和二烯丙基三硫化物（DATS），是薤白蔬菜的典型风味成分，在动物模型中已被证明可抑制苯并[a]芘（B[a]P）诱导的致癌作用。作为这种抑制作用的可能机制，我们使用人肝癌细胞模型（HepG2）研究了这些挥发性物质对细胞色素 P450 (CYP)1（CYP1A1、1A2 和 1B1）介导的 B[a]P 生物活化的影响。在 100-1,000 μM 浓度下，DADS 和 DATS 对 B[a]P 诱导的乙氧基瑞香素 O-脱乙基酶（EROD）活性（一种 CYP1 的标记酶）的抑制率分别为 30%-90% 和 70%-95%。细胞存活率是抑制 B[a]P 生物活化能力的指标，100-1,000 μM DADS 和 10-100 μM DATS 处理可提高细胞存活率。免疫印迹结果表明，B[a]P 诱导的 CYP1A2 蛋白受到 100-1,000 μM 的 DADS 和 10-100 μM 的 DATS 的抑制，但在任何微粒体中都检测不到 CYP1A1 和 1B1。对 B[a]P 代谢物的分析表明，与对照组相比，在 DADS 和 DATS 处理过的微粒体中形成的 7,8-二醇水平明显降低。烯丙基硫醚处理也降低了形成的 9,10-二醇和 4,5-二醇的水平。这些结果表明，烯丙基硫醚对 B[a]P 诱导的癌变的保护机制可能与调节 CYP1 介导的 B[a]P 生物活化有关。
• Yeast strains with stable integration of heterologous genes
  申请人：Centre National De La Recherche Scientifique

  公开号：US05635369A1

  公开（公告）日：1997-06-03

  Yeast strains and a method of expression in yeast of the monooxygenase activity of heterologous cytochromes P450 are disclosed. Within the genome of the yeast strain, genes for NADPH-cytochrome P450 reductase and cytochrome b5 are stably integrated and coexpressed. The genome is transformed with a plasmid carrying a cassette for the expression of a heterologous P450 gene.

  本发明涉及酵母菌株及其在酵母菌中表达异源细胞色素P450单加氧酶活性的方法。在酵母菌株的基因组中，稳定地整合和共同表达了NADPH-细胞色素P450还原酶和细胞色素b5的基因。该基因组经转化，携带有表达异源P450基因的盒式质粒。
• Interception of Benzo[<i>a</i>]pyrene-7,8-dione by UDP Glucuronosyltransferases (UGTs) in Human Lung Cells
  作者：Li Zhang、Meng Huang、Ian A. Blair、Trevor M. Penning

  DOI：10.1021/tx400268q

  日期：2013.10.21

  Polycyclic aromatic hydrocarbons (PAHs) are environmental and tobacco carcinogens. Proximate carcinogenic PAR trans-dihydrodiols are activated by human aldo-keto reductases (AKRs) to yield electrophilic and redox-active o-quinones. Interconversion among benzo[a]pyrene (B[a]P)-7,8-dione, a representative PAR o-quinone, and its corresponding catechol generates a futile redox-cycle with the concomitant production of reactive oxygen species (ROS). We investigated whether glucuronidation of B[a]P-7,8-catechol by human UDP glucuronosyltransferases (UGTs) could intercept the catechol in three different human lung cells. RT-PCR showed that UGTIA1, 1A3, and 2B7 were only expressed in human lung adenocarcinoma A549 cells. The corresponding recombinant UGTs were examined for their kinetic constants and product profile using B[a]P-7,8-catechol as a substrate. B[a]P-7,8-dione was reduced to B[a]P-7,8-catechol by dithiothreitol under anaerobic conditions and then further glucuronidated by the UGTs in the presence of uridine-5'-diphosphoglucuronic acid as a glucuronic acid group donor. UGT1A1 catalyzed the glucuronidation of B[a]P-7,8-catechol and generated two isomeric O-monoglucuronsyl-B[a]P-7,8-catechol products that were identified by RP-HPLC and by LC-MS/MS. By contrast, UGT1A3 and 2B7 catalyzed the formation of only one monoglucuronide, which was identical to that formed in A549 cells. The kinetic profiles of three UGTs followed Michaelis-Menten kinetics. On the basis of the expression levels of UGT1A3 and UGT2B7 and the observation that a single monoglucuronide was produced in A549 cells, we suggest that the major UGT isoforms in A549 cells that can intercept B[a]P-7,8-catechol are UGT1A3 and 2B7.