trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,j]acridine | 105500-28-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,j]acridine
• 英文别名: (18S,19R,20R,22S)-21-oxa-13-azahexacyclo[12.9.0.03,12.04,9.017,23.020,22]tricosa-1(14),2,4,6,8,10,12,15,17(23)-nonaene-18,19-diol
• CAS: 105500-28-5
• 化学式: C₂₁H₁₅NO₃
• 分子量: 329.355
• InChiKey: PIJVASQAQLIDRI-JSXRDJHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  65.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,j]acridine 在 sodium perchlorate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (1S,2S,3R,4S)-1,2,3,4-Tetrahydro-dibenzo[a,j]acridine-1,2,3,4-tetraol 、 (1R,2S,3R,4S)-1,2,3,4-Tetrahydrodibenzo[a,j]acridine-1,2,3,4-tetrol
  参考文献：
  名称：

  Sayer; Lehr; Kumar, Journal of the American Chemical Society, 1990, vol. 112, # 3, p. 1177 - 1185

  摘要：

  DOI：
• 作为产物：
  描述：

  反式-二苯并(a,j)吖啶-3,4-二氢二醇 在 间氯过氧苯甲酸 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以5.9 mg的产率得到trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,j]acridine
  参考文献：
  名称：

  Sayer; Lehr; Kumar, Journal of the American Chemical Society, 1990, vol. 112, # 3, p. 1177 - 1185

  摘要：

  DOI：

文献信息

• Sayer; Lehr; Kumar, Journal of the American Chemical Society, 1990, vol. 112, # 3, p. 1177 - 1185
  作者：Sayer、Lehr、Kumar、Yagi、Yeh、Holder、Duke、Silverton、Gibson、Jerina

  DOI：——

  日期：——
• <i>trans-</i>3,4-Dihydroxy-<i>anti</i>-1,2-epoxy-1,2,3,4-tetrahydrodi- benz[a,j]acridine Involvement in Dibenz[a,j]acridine DNA Adduct Formation in Mouse Skin Consistent with Ha-<i>ras</i> Mutation Patterns in Tumors
  作者：Weiling Xue、Joanne Schneider、Kent Mitchell、Marlene Jaeger、Vajira Nanayakkara、Glenn Talaska、David Warshawsky

  DOI：10.1021/tx010014y

  日期：2001.7.1

  Dibenz[a,j]acridine (DBA), is a N-heteropolycyclic aromatic environmental carcinogen found in complex combustion mixtures. The major route of DBA metabolic activation is reportedly through the trans-3,4-dihydroxy-3,4-dihydroDBA (DBA-3,4-DHD). The present studies were undertaken to determine the role of trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydroDBA (DBADE) in DBA activation pathway(s), the DNA bases involved in the binding of DBA to DNA, and whether the adducts produced are consistent with the mutation pattern in the Ha-ras gene. DBA (300 mug) or 50 mug synthesized (+/-)-DBADE was applied to the back of female Hsd:ICR(Br) mice. The mice were sacrificed 48 h later, and skin DNA was isolated, hydrolyzed, and analyzed with P-32-postlabeling. Of the four adducts produced in vivo, adduct 1 was the major adduct for DBA (> 50%) and adduct 2 was the major adduct for DBADE (89%). After the reaction of (+/-)-DBADE with purine nucleotides or calf thymus (CT) DNA in vitro, 100% of the DBADE-2 ' -dAMP adducts and 94% of DBADE-CT DNA adducts were chromatographically identical on TLC with adduct 2 and 86% of the DBADE-2 ' -dGMP adducts were chromatographically consistent with adduct 1 by 32P-postlabeling. Papillomas were induced on the backs of mice by a single application of 0.2 mu mol of DBA followed by twice-weekly application of 12-o-tetra-decanoylphorbol-13-acetate (TPA, 2 mug) for 24-26 weeks. Skin carcinomas were induced by twice weekly applications of DBA (0.1 mu mol) on the backs of mice. A to T and G to T transversions were found in codons 12, 13, and 61 of the Ha-ras gene in the treated mouse skin carcinoma and papilloma DNA, The mutational spectra in the Ha-ras gene are consistent with the DNA binding of DBA to dG or dA in vivo. Thus, this research has indicated that DBADE plays an important role in DBA metabolic activation and DNA binding in mouse skin, and an alternative pathway through a bis-dihydrodiol-epoxide of DBA may also be involved.