3-[[(5S,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]oxy]-N'-methylsulfonylpropanimidamide | 1310349-15-5

• 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: 3-[[(5S,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]oxy]-N'-methylsulfonylpropanimidamide
• CAS: 1310349-15-5
• 化学式: C₂₆H₃₀N₂O₁₀S
• 分子量: 562.598
• InChiKey: SANWQXVKUKJFQJ-CPUMGYLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  163
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  4β-O-propargylpodophyllotoxin 、 甲烷磺酰基叠氮化物 在 copper(l) iodide 、 氨 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以74%的产率得到3-[[(5S,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]oxy]-N'-methylsulfonylpropanimidamide
  参考文献：
  名称：

  Synthesis and biological evaluation of a series of podophyllotoxins derivatives as a class of potent antitubulin agents

  摘要：

  A series of eight novel podophyllotoxin derivatives were designed, synthesized and evaluated for biological activities. The antiproliferative activities were tested against a panel of human cancer cell lines (1(562, SGC, Hela and HepG) and the inhibition of tubulin polymerization was also evaluated. Compound 8e displayed significant antiproliferative activities for all four cell lines and strong levels of tubulin polymerization inhibition effect. Combined with cell apoptosis and cell cycle analysis, it demonstrated that compound 3e that effectively interfere with tubulin dynamics prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually dose dependent apoptosis. All experimental measurements were also supported by molecular docking simulations of colchicine binding site, which revealed the governing forces for the binding behavior and a good relationship with anti-tubulin activity and antiproliferative activities. The synthesis and biological studies provided an interesting new class of antitubulin agents for development of lead compounds and also a direction for further structure modification to obtain more potent anti-cancer drugs. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.009

文献信息

• Synthesis and biological evaluation of a series of podophyllotoxins derivatives as a class of potent antitubulin agents
  作者：Yingqian Liu、Dongfeng Wei、Yonglong Zhao、Weidong Cheng、Yan Lu、Yaqiong Ma、Xin Li、Chao Han、Yanxia Wei、Huiming Cao、Chunyan Zhao

  DOI：10.1016/j.bmc.2012.09.009

  日期：2012.11

  A series of eight novel podophyllotoxin derivatives were designed, synthesized and evaluated for biological activities. The antiproliferative activities were tested against a panel of human cancer cell lines (1(562, SGC, Hela and HepG) and the inhibition of tubulin polymerization was also evaluated. Compound 8e displayed significant antiproliferative activities for all four cell lines and strong levels of tubulin polymerization inhibition effect. Combined with cell apoptosis and cell cycle analysis, it demonstrated that compound 3e that effectively interfere with tubulin dynamics prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually dose dependent apoptosis. All experimental measurements were also supported by molecular docking simulations of colchicine binding site, which revealed the governing forces for the binding behavior and a good relationship with anti-tubulin activity and antiproliferative activities. The synthesis and biological studies provided an interesting new class of antitubulin agents for development of lead compounds and also a direction for further structure modification to obtain more potent anti-cancer drugs. (C) 2012 Elsevier Ltd. All rights reserved.