2,2'-[1,2-ethanediylbis(imino-2,1-ethanediyl)]-bis[5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione] | 150358-61-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2,2'-[1,2-ethanediylbis(imino-2,1-ethanediyl)]-bis[5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione]
• 英文别名: 5-Nitro-2-[2-[2-[2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)ethylamino]ethylamino]ethyl]benzo[de]isoquinoline-1,3-dione
• CAS: 150358-61-5
• 化学式: C₃₀H₂₄N₆O₈
• 分子量: 596.556
• InChiKey: RZJSJPYMWLAWOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  191
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-硝基-1,8-萘二甲酸酐 、 三乙烯四胺 以 乙醇 、 甲苯 为溶剂， 反应 4.0h， 以75%的产率得到2,2'-[1,2-ethanediylbis(imino-2,1-ethanediyl)]-bis[5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione]
  参考文献：
  名称：

  Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors

  摘要：

  A series of bisnaphthalimide derivatives were synthesized and evaluated for growth-inhibitory property against HT-29 human colon carcinoma. The N, N '-bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)] propane-2-ethanediamine (9) and the N, N '-Bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)] butylaminoethyl]-2-propanediamine (12) derivatives emerged as the most potent compounds of this series. Molecular modelling studies indicated that the high potency of 12, the most cytotoxic compound of the whole series, could be due to larger number of intermolecular interactions and to the best position of the naphthalimido rings, which favours pi-pi stacking interactions with purine and pyrimidine bases in the DNA active site. Moreover, 12 was designed as a DNA topoisomerase II poison and biochemical studies showed its effect on human DNA topoisomerase II. We then selected the compounds with a significant cytotoxicity for apoptosis assay. Derivative 9 was able to induce significantly apoptosis (40%) at 0.1 mu M concentration, and we demonstrated that the effect on apoptosis in HT-29 cells is mediated by caspases activation. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.024

文献信息

• HIGHLY WATER SOLUBLE BIS-NAPHTHALIMIDES USEFUL AS ANTICANCER AGENTS
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：EP0618901A1

  公开（公告）日：1994-10-12
• US5488110A
  申请人：——

  公开号：US5488110A

  公开（公告）日：1996-01-30
• [EN] HIGHLY WATER SOLUBLE BIS-NAPHTHALIMIDES USEFUL AS ANTICANCER AGENTS
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：WO1993012092A1

  公开（公告）日：1993-06-24

  (EN) This invention relates to bis-naphthalimides, including 2,2'-[1,2-ethanediylbis(methylimino-2,1-ethanediyl)]-bis[5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione], 2-[2-[N-methyl-N-[2-[[2-(5-nitro-1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-yl)ethyl]amino]ethyl]amino]ethyl]-5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione, 2,2'-[1,2-ethanediylbis(imino-2,1-ethanediyl)]-bis[5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione], pharmaceutical compositions containing them, and methods of using them to treat solid tumor carcinomas in mammals.(FR) Cette invention concerne des bis-naphtalimides telles que du 2,2'-[1,2-éthanediylbis(méthylimino-2,1-éthanediyle)]-bis[5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione], du 2-[2-[N-méthyle-N-[2-[[2-5-nitro-1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-yle)éthyle]amino]éthyle]amino]éthyle]-5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione, du 2,2'-[1,2-éthanediylbis(imino-2,1-éthanediyle)]-bis[5-nitro-1H-benz[de]isoquinoline-1,3(2H)-dione]; des compositions pharmaceutiques renfermant ces composés, ainsi que des procédés d'utilisations desdits composés pour traiter des carcinomes à tumeur solide chez des mammifères.
• Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors
  作者：Rosanna Filosa、Antonella Peduto、Simone Di Micco、Paolo de Caprariis、Michela Festa、Antonello Petrella、Giovanni Capranico、Giuseppe Bifulco

  DOI：10.1016/j.bmc.2008.11.024

  日期：2009.1

  A series of bisnaphthalimide derivatives were synthesized and evaluated for growth-inhibitory property against HT-29 human colon carcinoma. The N, N '-bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)] propane-2-ethanediamine (9) and the N, N '-Bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)] butylaminoethyl]-2-propanediamine (12) derivatives emerged as the most potent compounds of this series. Molecular modelling studies indicated that the high potency of 12, the most cytotoxic compound of the whole series, could be due to larger number of intermolecular interactions and to the best position of the naphthalimido rings, which favours pi-pi stacking interactions with purine and pyrimidine bases in the DNA active site. Moreover, 12 was designed as a DNA topoisomerase II poison and biochemical studies showed its effect on human DNA topoisomerase II. We then selected the compounds with a significant cytotoxicity for apoptosis assay. Derivative 9 was able to induce significantly apoptosis (40%) at 0.1 mu M concentration, and we demonstrated that the effect on apoptosis in HT-29 cells is mediated by caspases activation. (c) 2008 Elsevier Ltd. All rights reserved.