3,8,9-trimethoxyisoindolo[2,1-a]quinoxalin-6(5H)-imine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3,8,9-trimethoxyisoindolo[2,1-a]quinoxalin-6(5H)-imine
• 英文别名: 3,8,9-Trimethoxyisoindolo[2,1-a]quinoxalin-6-amine；3,8,9-trimethoxyisoindolo[2,1-a]quinoxalin-6-amine
• 化学式: C₁₈H₁₇N₃O₃
• 分子量: 323.351
• InChiKey: BOLIQLNPFPACMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-溴-4,5-二甲氧基苄醇 在 正丁基锂 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 sodium hydrogensulfite 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 28.75h， 生成 3,8,9-trimethoxyisoindolo[2,1-a]quinoxalin-6(5H)-imine
  参考文献：
  名称：

  Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action

  摘要：

  Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2'-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI(50) values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progression and inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated impairment of tubulin polymerization at pharmacologically significant concentrations of tested compounds. In addition, impaired DNA topoisomerase I functions and perturbation in telomere architecture were observed in cells exposed to micromolar concentrations of IIQ derivatives. The above results suggest that IIQ derivatives exhibit multi-target cytotoxic activities. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.005

文献信息

• Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action
  作者：Barbara Parrino、Anna Carbone、Cristina Ciancimino、Virginia Spanò、Alessandra Montalbano、Paola Barraja、Girolamo Cirrincione、Patrizia Diana、Claudia Sissi、Manlio Palumbo、Odra Pinato、Marzia Pennati、Giovanni Beretta、Marco Folini、Peter Matyus、Balázs Balogh、Nadia Zaffaroni

  DOI：10.1016/j.ejmech.2015.03.005

  日期：2015.4

  Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2'-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI(50) values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progression and inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated impairment of tubulin polymerization at pharmacologically significant concentrations of tested compounds. In addition, impaired DNA topoisomerase I functions and perturbation in telomere architecture were observed in cells exposed to micromolar concentrations of IIQ derivatives. The above results suggest that IIQ derivatives exhibit multi-target cytotoxic activities. (C) 2015 Elsevier Masson SAS. All rights reserved.