trans-4,5-dihydroxy-4,5-dihydro-benzo[a]pyrene | 37571-88-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: trans-4,5-dihydroxy-4,5-dihydro-benzo[a]pyrene
• 英文别名: trans-4,5-Dihydroxy-4,5-dihydro-benzopyren；trans-4,5-Dihydrobenzopyren-4,5-diol-6-T；trans-4,5-Dihydrobenzo[a]pyren-4,5-diol-6-T；trans-(-)-4,5-Dihydrobenzo(a)pyrene-4,5-diol；(4S,5S)-4,5-dihydrobenzo[a]pyrene-4,5-diol
• CAS: 37571-88-3
• 化学式: C₂₀H₁₄O₂
• 分子量: 286.33
• InChiKey: OYOQHRXJXXTZII-PMACEKPBSA-N

物化性质

• 熔点：
  210 °C(Solv: chloroform (67-66-3))
• 沸点：
  388.69°C (rough estimate)
• 密度：
  1.1197 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

SDS

反应信息

• 作为产物：
  描述：

  苯并[Pqr]四苯e-4,5-二酮 在 sodium tetrahydroborate 、 氧气 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以78%的产率得到trans-4,5-dihydroxy-4,5-dihydro-benzo[a]pyrene
  参考文献：
  名称：

  K-Regiontrans-Dihydrodiols of Polycyclic Arenes; An Efficient and Convenient Preparation fromo-Quinones oro-Diphenols by Reduction with Sodium Borohydride in the Presence of Oxygen

  摘要：

  DOI：

  10.1055/s-1982-29834

文献信息

• Influence of Na⁺ on DNA Reactions with Aromatic Epoxides and Diol Epoxides:  Evidence That DNA Catalyzes the Formation of Benzo[<i>a</i>]pyrene and Benz[<i>a</i>]anthracene Adducts at Intercalation Sites
  作者：Harshica Fernando、Chao-Ran Huang、Ann Milliman、Luchuan Shu、Pierre R. LeBreton

  DOI：10.1021/tx960134j

  日期：1996.1.1

  BP metabolites. DNA adducts, which account for less than 10% of the yields, also form. For BPDE in 0.20 mM ctDNA, k decreases 5.1 times as the Na+ concentration increases from 2.0 to 100 mM. Nevertheless, the DNA adduct level remains constant over the range of Na+ concentrations examined. These results provide evidence that, for BPDE in 0.20 mM DNA and 2.0 mM Na+, ctDNA adduct formation follows a mechanism

  苯并[a] py（BP）和苯并[a]蒽（BA）代谢产物，（+/-）-trans-7 8-二羟基-抗-9、10-环氧-7、8、9、10的反应-四氢-BP（BPDE），（+/-）-trans-3，4-二羟基-反-1,2-环氧-1,2,3,4-四氢-BA（BADE），（+/-）在伪一阶条件下，在变化的Na +（2.0-100 Mm）和天然浓度下，检查了-BP-4,5-氧化物（BPO）和（+/-）-BA-5、6-氧化物（BAO）小牛胸腺DNA（ctDNA）浓度。在0.2 mM的ctDNA和2.0 mM的Na +中，pH值为7.3时，大多数BPDE，BADE，BPO和BAO（87-95％）都会经历DNA催化的水解或重排。对于BPDE和BPO，2.0 mM Na +和0.2 mM ctDNA中的总体伪一级速率常数k比不使用DNA获得的值大21-72倍。对于BADE和BAO，速率常数受DNA的影响较小。k值为0。2
• Oxidation of Benzo[a]pyrene by Recombinant Human Cytochrome P450 Enzymes
  作者：Eckhart Bauer、Zuyu Guo、Yune-Fang Ueng、L. Chastine Bell、Darryl Zeldin、F. Peter Guengerich

  DOI：10.1021/tx00043a018

  日期：1995.1

  The oxidation of benzo[a]pyrene (B[a]P) was examined using reconstituted systems prepared with recombinant human cytochrome P450 (P450) enzymes 1A1, 1A2, 2C8, 2C10, 2E1, and 3A4 and with microsomes prepared from Saccharomyces cerevisiae expressing recombinant human P450s 2C8, 2C9, and 2C18. Products measured by HPLC included the 3- and 9-phenols, the 4,5-, 7,8-, and 9,10-dihydrodiols (detected in the presence of epoxide hydrolase), and products in the polar fraction eluting immediately after the void volume. The most active enzyme in all reactions was P450 1A1. P450 3A4 and P450 1A2 formed appreciable amounts of several of the products, including the 3-phenol. P450 2C enzymes and P450 2E1 formed relatively low amounts of all B[a]P products. Consideration of these patterns along with knowledge of levels of expression of the P450s in human tissues and previous results with microsomes leads to the conclusion that P450 1A1 should dominate the oxidation of B[a]P in tissues where it is present and inducible. In human liver the level of P450 1A1 is low and P450 3A4, P450 2C subfamily enzymes, and P450 1A2 probably all contribute. Of the human P450s considered here, P450 1A2 was the most active hepatic enzyme forming the 7,8-dihydrodiol. 7,8-Benzoflavone stimulated the oxidation of B[a]P by P450 3A4 and inhibited the oxidations catalyzed by P450 1A2. The extent of inhibition of P450 1A1 was less (than with P450 1A2), probably due to the rapid oxidation of 7,8-benzoflavone by P450 1A1. The major 7,8-benzoflavone product appears to be the 5,6-oxide.
• Photoemission probes of catalysis of benzo[a]pyrene epoxide reactions in complexes with linear, double-stranded and closed-circular, single-stranded DNA
  作者：Chao Ran Huang、Ann Milliman、Harry L. Price、Shigeyuki Urano、Sharon M. Fetzer、Pierre R. LeBreton

  DOI：10.1021/ja00070a028

  日期：1993.8

  Fluorescence intensity measurements of overall, pseudo-first-order rate constants for two epoxide-containing metabolites of benzo[a]pyrene (BP) were carried out in Tris, EDTA buffer (pH 7.3) without DNA, and in buffer with double-stranded calf thymus DNA (DS ctDNA) and with closed-circular, single-stranded viral M13mp19 DNA (SS M13 DNA). Highly purified SS M13 DNA was employed in order to avoid polymeric contamination which is present in DNA samples obtained using a standard preparation method relying on phenol extraction and which influences results from measurements of DNA-ligand interactions. The BP metabolites examined were highly carcinogenic (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and less genotoxic benzo[a]pyrene 4,5-oxide (BPO). Without DNA, BPDE hydrolyzes to 7,8,9,10-tetrahydroxytetrahydro-BP, while BPO hydrolyzes to trans-4,5-dihydroxy-4,5-dihydro-BP(BP45D) and rearranges to 4-hydroxy-BP. With DNA, BPDE and BPO hydrolysis and rearrangement are catalyzed, and DNA modification occurs. In DS ctDNA, previous kinetic and binding measurements indicate that catalysis occurs primarily at intercalation sites. In SS M13 DNA (0.20 mM), BPDE has overall, pseudo-first-order rate constants (k) of (12 +/- 1) X 10(-3) and (2.8 +/- 0.5) X 10(-3) s-1, at Na+ concentrations of 2.0 and 100 mM, respectively. At these Na+ concentrations, values of k measured in SS M13 DNA are 3-16 times larger than values measured without DNA, but smaller than values measured in DS ctDNA. For BPO, the ordering of k values without DNA, with SS M13 DNA, and with DS ctDNA is the same as for BPDE. At 2.0 mM Na+, the nonreactive diols, trans-7,8-dihydroxy-7,8-dihydro-BP (BP78D) and BP45D, which are model compounds for BPDE and BPO, respectively, have SS M13 DNA association constants [(7.2 +/- 0.5) X 103 and (2.7 +/- 0.5) X 10(3) M-1] that are 2.3 times smaller than DS ctDNA association constants. In contrast, at 100 mM Na+, association constants for SS M13 DNA are 2.9-3.1 times larger than for DS ctDNA. Fluorescence lifetime measurements indicate that, in SS M13 DNA, reversible binding involves intercalation into local duplex regions. Estimated catalytic rate constants (k(cat)) for BPDE hydrolysis in SS M13 DNA, obtained from BP78D association constants and from k values measured with and without DNA, are (22.8 +/- 2.5) X 10(-3) and (3.5 +/- 0.7) X 10(-3) s-1, at 2.0 and 100 mM Na+, respectively. For this Na+ concentration range, the ratio of k(cat) values for DS ctDNA versus SS M13 DNA is almost constant (1.7 +/- 0.6) even though the absolute k(cat) values vary by more than a factor of 5. The similar magnitudes of k(cat) values for SS M13 DNA and DS ctDNA provide evidence that catalytic sites in SS M13 DNA are similar to intercalated catalytic sites in DS ctDNA.
• Photoemission probes of hydrocarbon-DNA interactions: a comparison of DNA influences on the reactivities of (.+-.)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, benzo[a]pyrene 4,5-oxide, and benz[a]anthracene 5,6-oxide
  作者：Shigeyuki Urano、Harry L. Price、Sharon M. Fetzer、Anita V. Briedis、Ann Milliman、Pierre R. LeBreton

  DOI：10.1021/ja00010a033

  日期：1991.5

  Time-resolved fluorescence and UV photoelectron measurements have been employed to examine the influence of calf thymus DNA on the reactivities of epoxides derived from benzo[a]pyrene (BP) and benz[a]anthracene (BA). By monitoring the increase in fluorescence intensity, which accompanies reaction at 23-degrees-C, overall, pseudo-first-order rate constants have been measured for reactions of the highly carcinogenic bay region epoxide (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and of two less carcinogenic K region epoxides benzo[a]pyrene 4,5-oxide (BPO) and benz[a]anthracene 5,6-oxide (BAO). Overall rate constants for hydrolysis and rearrangement reactions have been measured for BPDE, BPO, and BAO in buffer alone (1.0 mM sodium cacodylate, pH 7.1). The rate constants increase in the order BPO ((3.8 +/- 0.1) x 10(-6) s-1) < BAO ((5.7 +/- 2.6) x 10(-5) s-1) < BPDE ((7.2 +/- 1.0) x 10(-4) s-1). These results have been compared with overall rate constants for reactions, carried out in calf thymus DNA, which result in catalyzed hydrolysis and rearrangement, as well as DNA adduct formation. In DNA, the ordering of the rate constants for BPO and BAO changes from that observed in buffer alone. The rate constants increase in the order BAO ((2.8 +/- 0.1) x 10(-3) s-1) < BPO ((1.2 +/- 0.2) x 10(-2) s-1) < BPDE (approximately 1 x 10(-1) s-1). This ordering is the same as the ordering of association constants for the reversible binding to DNA of the fluorescent diols trans-7,8-dihydroxy-7,8-dihydro-BP (BP78D), trans-4,5-dihydroxy-4,5-dihydro-BP (BP45D) and cis-5,6-dihydroxy-5,6-dihydro-BA (BAD), which are model compounds of BPDE, BPO, and BAO, respectively. For the model compounds, the association constants for intercalation increase in the order BAD ((3.6 +/- 0.9( x 10(2) M-1) < BP45D ((9.6 +/- 0.5) x 10(3) M-1) < BP78D ((3.4 +/- 0.1) x 10(4) M-1). This ordering is consistent with the ordering of the association constants of BPDE ((2.5 +/- 0.3) x 10(4) M-1) and of BPO ((6.0 +/- 1.0) x 10(3) M-1). The temperature dependence of the association constants of the model compounds demonstrates that, for the intercalation of the BP diols into DNA, differences in the enthalpy of binding contribute significantly to differences in the free energy of binding. UV photoelectron data and results from ab initio molecular orbital calculations on BPDE, BPO, and BAO indicate that, for these three epoxides, the association constants increase as the ionization potentials decrease and the polarizabilities increase. The percentage of epoxide reaction that yields DNA adducts has been compared under varying conditions. For long reaction times (> 1 h) in systems containing native, calf thymus DNA at low salt concentrations, the ordering of adduct yields is BPO (14.9 +/- 1.1%) > BPDE (10.1 +/- 3.0%) > BAO (3.6 +/- 0.4%). For short reaction times (10 min) in systems containing native DNA stabilized with 0.10 mM Mg2+, the ordering of adduct yields is BPDE (7.3 +/- 1.9%) > BPO (1.3 +/- 0.1%) > BAO (0.1 +/- 0.1%). These results suggest that the ability of an epoxide to form adducts with exposed DNA during long reaction times is less indicative of the genotoxic potency of the epoxide than its ability to form adducts with stabilized DNA during short reaction times.
• Multi-stage stem cell carcinogenesis
  申请人：Krtolica Ana

  公开号：US20100162416A1

  公开（公告）日：2010-06-24

  The present invention relates to a system of multi-stage stem cell carcinogenesis and a method of generating such multi-stage stem cell carcinogenesis system. Various stages of cancer stem cells can be generated from normal stem cells via mutagenesis. The system of the present invention enables monitoring changes in the ability of cells to transition from one stage of carcinogenesis to another and to identify genetic pathways and molecules that influence carcinogenesis. The present invention also enables a high-throughput and nonbiased screening for targets that preferentially affect cancer stem cells relative to non-cancer stem cells or their derivatives during stem cell carcinogenesis, thus is useful in developing anti-cancer therapeutics.