7-(3-(dimethylamino)propyl)-10-methoxybenzo[a]phenazin-5(7H)-one

• 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: 7-(3-(dimethylamino)propyl)-10-methoxybenzo[a]phenazin-5(7H)-one
• 英文别名: 7-[3-(Dimethylamino)propyl]-10-methoxybenzo[a]phenazin-5-one；7-[3-(dimethylamino)propyl]-10-methoxybenzo[a]phenazin-5-one
• 化学式: C₂₂H₂₃N₃O₂
• 分子量: 361.444
• InChiKey: AHOONYPMXMDOEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  45.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氟-3-硝基苯甲醚 在 溶剂黄146 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 7-(3-(dimethylamino)propyl)-10-methoxybenzo[a]phenazin-5(7H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 7-alkylamino substituted benzo[a]phenazin derivatives as dual topoisomerase I/II inhibitors

  摘要：

  A novel series of benzo[a]phenazin derivatives bearing alkylamino side chains were designed, synthesized and evaluated for their topoisomerases inhibitory activity as well as cytotoxicity against four human cancer cell lines (HL-60, K-562, HeLa, and A549). These compounds were found to be dual inhibitors of topoisomerase (Topo) I and Topo II, and exhibited excellent antiproliferative activity, in particular against HL-60 cells with submicromolar IC50 values. Further mechanistic studies showed that this class of compounds acted as Topo I poisons by stabilizing the Topo I-DNA cleavage complexes and Topo II catalytic inhibitors by inhibiting the ATPase activity of hTopo II. Molecular docking studies revealed the binding modes of these compounds for Topo I and Topo II. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.024

文献信息

• Design, synthesis and biological evaluation of novel 7-alkylamino substituted benzo[a]phenazin derivatives as dual topoisomerase I/II inhibitors
  作者：Bing-Lei Yao、Yan-Wen Mai、Shuo-Bin Chen、Hua-Ting Xie、Pei-Fen Yao、Tian-Miao Ou、Jia-Heng Tan、Hong-Gen Wang、Ding Li、Shi-Liang Huang、Lian-Quan Gu、Zhi-Shu Huang

  DOI：10.1016/j.ejmech.2015.01.024

  日期：2015.3

  A novel series of benzo[a]phenazin derivatives bearing alkylamino side chains were designed, synthesized and evaluated for their topoisomerases inhibitory activity as well as cytotoxicity against four human cancer cell lines (HL-60, K-562, HeLa, and A549). These compounds were found to be dual inhibitors of topoisomerase (Topo) I and Topo II, and exhibited excellent antiproliferative activity, in particular against HL-60 cells with submicromolar IC50 values. Further mechanistic studies showed that this class of compounds acted as Topo I poisons by stabilizing the Topo I-DNA cleavage complexes and Topo II catalytic inhibitors by inhibiting the ATPase activity of hTopo II. Molecular docking studies revealed the binding modes of these compounds for Topo I and Topo II. (C) 2015 Elsevier Masson SAS. All rights reserved.