N-[(10S,11S,15R,16R)-16-(4-hydroxy-3,5-dimethoxyphenyl)-14-oxo-4,6,13-trioxatetracyclo[7.7.0.0(3,7).0(11,15)]hexadeca-1,3(7),8-trien-10-yl]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzamide | 1350264-36-6

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: N-[(10S,11S,15R,16R)-16-(4-hydroxy-3,5-dimethoxyphenyl)-14-oxo-4,6,13-trioxatetracyclo[7.7.0.0(3,7).0(11,15)]hexadeca-1,3(7),8-trien-10-yl]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzamide
• 英文别名: N-[(5S,5aS,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]-4-[3-(trifluoromethyl)diazirin-3-yl]benzamide
• CAS: 1350264-36-6
• 化学式: C₃₀H₂₄F₃N₃O₈
• 分子量: 611.531
• InChiKey: OUCQXMCHXQAMMH-LVEBQJTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  44
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  N-[(10S,11S,15R,16R)-16-(4-hydroxy-3,5-dimethoxyphenyl)-14-oxo-4,6,13-trioxatetracyclo[7.7.0.0(3,7).0(11,15)]hexadeca-1,3(7),8-trien-10-yl]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzamide 、 乙腈 反应 0.17h， 生成
  参考文献：
  名称：

  A diazirine-based photoaffinity etoposide probe for labeling topoisomerase II

  摘要：

  Etoposide is a widely used anticancer drug that targets topoisomerase II, an essential nuclear enzyme. However, despite the fact that it has been in use and studied for more than 30 years the specific site on the enzyme to which it binds is unknown. In order to identify the etoposide binding site(s) on topoisomerase II, a diazirine-based photoaffinity etoposide analog probe has been synthesized and its photoreactivity and biological activities have been characterized. Upon UV irradiation, the diazirine probe rapidly produced a highly reactive carbene species that formed covalent adducts containing stable carbon-based bonds indicating that it should also be able to form stable covalent adducts with amino acid residues on topoisomerase II. The human leukemia K562 cell growth and topoisomerase II inhibitory properties of the diazirine probe suggest that it targets topoisomerase II in a manner similar to etoposide. The diazirine probe was also shown to act as a topoisomerase II poison through its ability to cause topoisomerase II alpha-mediated double-strand cleavage of DNA. Additionally, the diazirine probe significantly increased protein-DNA covalent complex formation upon photoirradiation of diazirine probe-treated K562 cells, as compared to etoposide-treated cells. This result suggests that the photoactivated probe forms a covalent adduct with topoisomerase II alpha. In conclusion, the present characterization of the chemical, biochemical, and biological properties of the newly synthesized diazirine-based photoaffinity etoposide analog indicates that use of a proteomics mass spectrometry approach will be a tractable strategy for future identification of the etoposide binding site(s) on topoisomerase II through covalent labeling of amino acid residues. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.048
• 作为产物：
  描述：

  (5R,5aR,8aS,9S)-9-amino-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,5a,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(8H)-one 、 4-[3-(三氟甲基)-3H-双吖丙啶-3-基]苯甲酰氯 在 吡啶 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以41%的产率得到N-[(10S,11S,15R,16R)-16-(4-hydroxy-3,5-dimethoxyphenyl)-14-oxo-4,6,13-trioxatetracyclo[7.7.0.0(3,7).0(11,15)]hexadeca-1,3(7),8-trien-10-yl]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzamide
  参考文献：
  名称：

  A diazirine-based photoaffinity etoposide probe for labeling topoisomerase II

  摘要：

  Etoposide is a widely used anticancer drug that targets topoisomerase II, an essential nuclear enzyme. However, despite the fact that it has been in use and studied for more than 30 years the specific site on the enzyme to which it binds is unknown. In order to identify the etoposide binding site(s) on topoisomerase II, a diazirine-based photoaffinity etoposide analog probe has been synthesized and its photoreactivity and biological activities have been characterized. Upon UV irradiation, the diazirine probe rapidly produced a highly reactive carbene species that formed covalent adducts containing stable carbon-based bonds indicating that it should also be able to form stable covalent adducts with amino acid residues on topoisomerase II. The human leukemia K562 cell growth and topoisomerase II inhibitory properties of the diazirine probe suggest that it targets topoisomerase II in a manner similar to etoposide. The diazirine probe was also shown to act as a topoisomerase II poison through its ability to cause topoisomerase II alpha-mediated double-strand cleavage of DNA. Additionally, the diazirine probe significantly increased protein-DNA covalent complex formation upon photoirradiation of diazirine probe-treated K562 cells, as compared to etoposide-treated cells. This result suggests that the photoactivated probe forms a covalent adduct with topoisomerase II alpha. In conclusion, the present characterization of the chemical, biochemical, and biological properties of the newly synthesized diazirine-based photoaffinity etoposide analog indicates that use of a proteomics mass spectrometry approach will be a tractable strategy for future identification of the etoposide binding site(s) on topoisomerase II through covalent labeling of amino acid residues. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.048

文献信息

• A diazirine-based photoaffinity etoposide probe for labeling topoisomerase II
  作者：Gaik-Lean Chee、Jack C. Yalowich、Andrew Bodner、Xing Wu、Brian B. Hasinoff

  DOI：10.1016/j.bmc.2009.11.048

  日期：2010.1

  Etoposide is a widely used anticancer drug that targets topoisomerase II, an essential nuclear enzyme. However, despite the fact that it has been in use and studied for more than 30 years the specific site on the enzyme to which it binds is unknown. In order to identify the etoposide binding site(s) on topoisomerase II, a diazirine-based photoaffinity etoposide analog probe has been synthesized and its photoreactivity and biological activities have been characterized. Upon UV irradiation, the diazirine probe rapidly produced a highly reactive carbene species that formed covalent adducts containing stable carbon-based bonds indicating that it should also be able to form stable covalent adducts with amino acid residues on topoisomerase II. The human leukemia K562 cell growth and topoisomerase II inhibitory properties of the diazirine probe suggest that it targets topoisomerase II in a manner similar to etoposide. The diazirine probe was also shown to act as a topoisomerase II poison through its ability to cause topoisomerase II alpha-mediated double-strand cleavage of DNA. Additionally, the diazirine probe significantly increased protein-DNA covalent complex formation upon photoirradiation of diazirine probe-treated K562 cells, as compared to etoposide-treated cells. This result suggests that the photoactivated probe forms a covalent adduct with topoisomerase II alpha. In conclusion, the present characterization of the chemical, biochemical, and biological properties of the newly synthesized diazirine-based photoaffinity etoposide analog indicates that use of a proteomics mass spectrometry approach will be a tractable strategy for future identification of the etoposide binding site(s) on topoisomerase II through covalent labeling of amino acid residues. (C) 2009 Elsevier Ltd. All rights reserved.