二苯并(a,l)芘8,9-二氢二醇 | 130063-43-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 二苯并(a,l)芘8,9-二氢二醇
• 英文名称: cis-dibenzo[a,l]pyrene-8,9-diol
• 英文别名: Ccris 6332；hexacyclo[10.10.2.02,7.08,24.015,23.017,22]tetracosa-1(23),2,4,6,8(24),9,11,15,17,19,21-undecaene-13,14-diol
• CAS: 130063-43-3
• 化学式: C₂₄H₁₆O₂
• 分子量: 336.39
• InChiKey: NDCWEARXOFJOPX-UHFFFAOYSA-N

物化性质

• 沸点：
  644.3±55.0 °C(Predicted)
• 密度：
  1.454±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  二苯并(a,l)芘8,9-二氢二醇 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 为溶剂， 反应 168.0h， 生成 dibenzo[a,l]pyrene-8,9-quinone
  参考文献：
  名称：

  Metabolic Activation of Dibenzo[a,l]pyrene by Human Cytochrome P450 1A1 and P450 1B1 Expressed in V79 Chinese Hamster Cells

  摘要：

  Metabolic activation of the strongly carcinogenic polycyclic aromatic hydrocarbon (PAH) dibenzo[a,l]pyrene (DB[a,l]P) and its trans-8,9-dihydrodiol (trans-8,9-diol) catalyzed by human cytochromes P450 (P450) 1A1 and 1B1 was investigated. DNA binding of DB[a,l]P in mammalian cell lines has previously been shown to be preferentially mediated by fjord region DB[a,l]P-11,12-dihydrodiol 13,14-epoxides (DB[a,l]PDE). In order to elucidate different capabilities of both P450 enzymes for metabolic activation of DB[a,l]P V79 Chinese hamster cells, stably expressing human P450s 1A1 or 1B1 have been exposed to the parent PAH or its racemic trans-8,9-diol. For this purpose, synthesis and spectroscopic characterization of the trans-DB-[a,l]P-8,9-diol and its individual enantiomers have been achieved. Both human P450-expressing cell lines were capable of transforming DB[a,l]P to its fjord region DB[a,l]PDE, but the extent of metabolism to DB[a,l]PDE catalyzed by human P450 1B1 was higher compared to human P450 1A1 at all times measured. On the other hand, cytotoxicity studies performed with the same incubation systems emerged stronger effects by DB[a,l]P and its enantiomeric trans-11,12-diols in human P450 1A1-expressing cells. Both human P450 enzymes stereospecifically catalyzed the formation of the (-)-DB[a,l]P-11,12-diol with R,R-configuration, whereas only the human P450 1A1-expressing cells form small amounts of the K-region trans-8,9-diol with high excess of the (+)-(8R,9R)-enantiomer. Application of trans-DB[a,l]P-8,9-diol in metabolism studies revealed that this compound is converted by human P450s 1A1 and 1B1 to several diol phenols and bis-diols. However, and even at concentrations as high as 10 mu M, in both cell lines the trans-DB[a,l]P-8,9-diol showed no cytotoxicity at all, suggesting that an activation of DB[a,l]P via further oxidation of the K-region trans-8,9-diol plays a minor role.

  DOI：

  10.1021/tx980240g
• 作为产物：
  描述：

  二苯并(A,L)芘 在 四氧化锇 、 sodium hydrogen sulfate 作用下， 以 吡啶 为溶剂， 反应 145.0h， 生成 二苯并(a,l)芘8,9-二氢二醇
  参考文献：
  名称：

  Metabolic Activation of Dibenzo[a,l]pyrene by Human Cytochrome P450 1A1 and P450 1B1 Expressed in V79 Chinese Hamster Cells

  摘要：

  Metabolic activation of the strongly carcinogenic polycyclic aromatic hydrocarbon (PAH) dibenzo[a,l]pyrene (DB[a,l]P) and its trans-8,9-dihydrodiol (trans-8,9-diol) catalyzed by human cytochromes P450 (P450) 1A1 and 1B1 was investigated. DNA binding of DB[a,l]P in mammalian cell lines has previously been shown to be preferentially mediated by fjord region DB[a,l]P-11,12-dihydrodiol 13,14-epoxides (DB[a,l]PDE). In order to elucidate different capabilities of both P450 enzymes for metabolic activation of DB[a,l]P V79 Chinese hamster cells, stably expressing human P450s 1A1 or 1B1 have been exposed to the parent PAH or its racemic trans-8,9-diol. For this purpose, synthesis and spectroscopic characterization of the trans-DB-[a,l]P-8,9-diol and its individual enantiomers have been achieved. Both human P450-expressing cell lines were capable of transforming DB[a,l]P to its fjord region DB[a,l]PDE, but the extent of metabolism to DB[a,l]PDE catalyzed by human P450 1B1 was higher compared to human P450 1A1 at all times measured. On the other hand, cytotoxicity studies performed with the same incubation systems emerged stronger effects by DB[a,l]P and its enantiomeric trans-11,12-diols in human P450 1A1-expressing cells. Both human P450 enzymes stereospecifically catalyzed the formation of the (-)-DB[a,l]P-11,12-diol with R,R-configuration, whereas only the human P450 1A1-expressing cells form small amounts of the K-region trans-8,9-diol with high excess of the (+)-(8R,9R)-enantiomer. Application of trans-DB[a,l]P-8,9-diol in metabolism studies revealed that this compound is converted by human P450s 1A1 and 1B1 to several diol phenols and bis-diols. However, and even at concentrations as high as 10 mu M, in both cell lines the trans-DB[a,l]P-8,9-diol showed no cytotoxicity at all, suggesting that an activation of DB[a,l]P via further oxidation of the K-region trans-8,9-diol plays a minor role.

  DOI：

  10.1021/tx980240g

文献信息

• Metabolic Activation of Racemic and Enantiomeric <i>trans</i>-8,9-Dihydroxy-8,9-dihydrodibenzo[<i>a</i>,<i>l</i>]pyrene (Dibenzo[<i>def</i>,<i>p</i>]chrysene) to Dibenzo[<i>a</i>,<i>l</i>]pyrene-bis-dihydrodiols by Induced Rat Liver Microsomes and a Recombinant Human P450 1A1 System:  The Role of the K-Region-Derived Metabolic Intermediates in the Formation of Dibenzo[<i>a</i>,<i>l</i>]pyrene−DNA Adducts
  作者：Stephen Nesnow、Christine Davis、William Padgett、Michael George、Guy Lambert、Fabienne Meyers、Joycelyn Allison、Linda Adams、Leon C. King

  DOI：10.1021/tx9801561

  日期：1998.12.1

  Metabolic activation studies of dibenzo[a,l] pyrene (DB[a,l]P) (dibenzo[def,p] chrysene), an extremely potent environmental carcinogen, have been focused on metabolism at the fjord region, a region associated with high mutagenic and carcinogenic activities of the col rer;ponding fjord-region DB[a,l]P-11,12-diol-13,14-epoxides. DB[a,l]P is metabolized by beta-naphthoflavone (BNF)- and 3-methylcholanthrene-induced rat liver microsomes and a recombinant human P450 1A1 system to two major dihydrodiols, the K-region dihydrodiol, DB[a,l]P-8,9-dihydrodiol (DB[a,l]P-8,9-diol), and the fjord-region dihydrodiol, DB[a,l]P-11,12-dihydrodiol. We have investigated the further metabolic activation of BB[a,l]P-8,9-diol by BNF-induced rat liver microsomes and a recombinant human P450 1A1 system with epoxide hydrolase to DB[a,l]P- bis-diols and to DNA adducts. (+/-)-trans-DB[a,;]P-8,9-diol was synthesized and resolved into its enantiomers. Racemic trans-DB[a,l]P-8,9-diol was metabolized by BNF-induced rat liver microsomes to six metabolites: two diastereomers of trans,trans-DB[a,;l]P-8,9:11,12-bis-diol, two diastereomers of trans, cis-DB[a,l]P-8,9:11,12-bis-diol, and two diastereomers of trans-DB- [a,l]P-8,9:13,14-bis-diol as characterized by NMR, MS, and UV spectroscopy. Metabolic studies using both enantiomeric (-)- and (+)-trans-DB[a,l]P-8,9-diol further demonstrated that each diastereomer of trans,trans-DB[a,l]P-8,9:11,12-bis-diol and trans-DB[a,l]P-8,9:13,14-bis-diol was comprised of two enantiomers. Similarly, incubations of enantiomeric or racemic trans-DB[a,l]P-8,9-diol with a recombinant human P450 1A1 system and epoxide hydrolase also gave the same two enantiomeric mixtures of diastereomers of trans,trans-DB[a,l]P-8,9:11,12-bis-diol and the same two enantiomeric mixtures of diastereomers of trans-DB[a,l]P-8,9:13,14-bis diol. This suggested that the microsomal oxidations of (-)- and (+)-trans-DB[a,l]P-8,9-diol were stereospecific. The stereospecific formation of enantiomers of trans-DB[a,l]P-8,9-diol from DB[a,l]P was examined using both BNF-induced rat liver microsomes and a recombinant human P450 1A1 system with epoxide hydrolase, Stereospecificity was observed as both metabolic systems favored the formation of (-)-trans-DB[a,l]P-8,9-diol by 8-9-fold. DNA adduct studies were undertaken using TLC/HPLC P-32-postlabeling techniques. In the presence of a recombinant human P450 1A1, system with epoxide hydrolase, DB[a,l]P gave two groups of calf thymus DNA adducts. The group of later-eluting adducts were identified as at ising from syn- and anti-DB[a,l]P-11,12-diol-13-14-epoxides, while the more polar early-eluting adducts were derived, in part, from the further activation of trans-DB[a,l]P-8,9-diol. Our data indicate that, in P450 1A1-mediated microsomal incubations, DB[a,l]P is metabolized to trans-DB[a,l]P-8-9-diol which is further metabolized to DB[a,l]P-bis-diols. trans-DB[a,l]P-8,9-diol is metabolically activated to intermediates that can bind to DNA and give DNA adducts similar to those observed with DB[a,l]P. These results indicate that DB[a,l]P can be metabolically activated by both fjord-region and K-region pathways.
• Metabolic Activation of Dibenzo[<i>a</i>,<i>l</i>]pyrene by Human Cytochrome P450 1A1 and P450 1B1 Expressed in V79 Chinese Hamster Cells
  作者：Andreas Luch、Wolfgang Schober、Volker J. Soballa、Gottfried Raab、Helmut Greim、Jürgen Jacob、Johannes Doehmer、Albrecht Seidel

  DOI：10.1021/tx980240g

  日期：1999.4.1

  Metabolic activation of the strongly carcinogenic polycyclic aromatic hydrocarbon (PAH) dibenzo[a,l]pyrene (DB[a,l]P) and its trans-8,9-dihydrodiol (trans-8,9-diol) catalyzed by human cytochromes P450 (P450) 1A1 and 1B1 was investigated. DNA binding of DB[a,l]P in mammalian cell lines has previously been shown to be preferentially mediated by fjord region DB[a,l]P-11,12-dihydrodiol 13,14-epoxides (DB[a,l]PDE). In order to elucidate different capabilities of both P450 enzymes for metabolic activation of DB[a,l]P V79 Chinese hamster cells, stably expressing human P450s 1A1 or 1B1 have been exposed to the parent PAH or its racemic trans-8,9-diol. For this purpose, synthesis and spectroscopic characterization of the trans-DB-[a,l]P-8,9-diol and its individual enantiomers have been achieved. Both human P450-expressing cell lines were capable of transforming DB[a,l]P to its fjord region DB[a,l]PDE, but the extent of metabolism to DB[a,l]PDE catalyzed by human P450 1B1 was higher compared to human P450 1A1 at all times measured. On the other hand, cytotoxicity studies performed with the same incubation systems emerged stronger effects by DB[a,l]P and its enantiomeric trans-11,12-diols in human P450 1A1-expressing cells. Both human P450 enzymes stereospecifically catalyzed the formation of the (-)-DB[a,l]P-11,12-diol with R,R-configuration, whereas only the human P450 1A1-expressing cells form small amounts of the K-region trans-8,9-diol with high excess of the (+)-(8R,9R)-enantiomer. Application of trans-DB[a,l]P-8,9-diol in metabolism studies revealed that this compound is converted by human P450s 1A1 and 1B1 to several diol phenols and bis-diols. However, and even at concentrations as high as 10 mu M, in both cell lines the trans-DB[a,l]P-8,9-diol showed no cytotoxicity at all, suggesting that an activation of DB[a,l]P via further oxidation of the K-region trans-8,9-diol plays a minor role.