6-(2-hydroxyethylamino)-2-dodecyl-1H-benzo[de]isoquinoline-1,3(2H)-dione | 1207670-61-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 6-(2-hydroxyethylamino)-2-dodecyl-1H-benzo[de]isoquinoline-1,3(2H)-dione
• 英文别名: 2-Dodecyl-6-(2-hydroxyethylamino)benzo[de]isoquinoline-1,3-dione
• CAS: 1207670-61-8
• 化学式: C₂₆H₃₆N₂O₃
• 分子量: 424.583
• InChiKey: ORHCGLLHBQGMIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  31
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(2-hydroxyethylamino)-2-dodecyl-1H-benzo[de]isoquinoline-1,3(2H)-dione 在 四丁基溴化铵 、 三苯基膦 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 氯仿 为溶剂， 反应 72.0h， 生成 6-((2-(1,4,8,11-tetraazacyclotetradecan-1-yl)ethyl)amino)-2-dodecyl-1H-benzo[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  Antiproliferative and apoptosis-inducing activities of novel naphthalimide–cyclam conjugates through dual topoisomerase (topo) I/II inhibition

  摘要：

  A novel series of naphthalimide-cyclam conjugates were designed and synthesized. Among them, compounds 4c, 4d, 8c and 8d which bearing long lipophilic alkyl chains, displayed comparable or more potent cytotoxic activities against human tumor cell lines than amonafide. Furthermore, the four compounds were proved to possess strong inhibition against both topoisomerase I and II. The representative compound 8c exhibited moderate DNA intercalation activity. Molecular modeling studies identified the possible interaction of compound 8c with the molecular target by forming topoisomerase/DNA/drug ternary complex. Finally, derivatives with long lipophilic alkyl chains could efficiently induce apoptosis. (C) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.07.011
• 作为产物：
  描述：

  十二烷基伯胺 以 乙醇 、 乙二醇甲醚 为溶剂， 生成 6-(2-hydroxyethylamino)-2-dodecyl-1H-benzo[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  Antiproliferative and apoptosis-inducing activities of novel naphthalimide–cyclam conjugates through dual topoisomerase (topo) I/II inhibition

  摘要：

  A novel series of naphthalimide-cyclam conjugates were designed and synthesized. Among them, compounds 4c, 4d, 8c and 8d which bearing long lipophilic alkyl chains, displayed comparable or more potent cytotoxic activities against human tumor cell lines than amonafide. Furthermore, the four compounds were proved to possess strong inhibition against both topoisomerase I and II. The representative compound 8c exhibited moderate DNA intercalation activity. Molecular modeling studies identified the possible interaction of compound 8c with the molecular target by forming topoisomerase/DNA/drug ternary complex. Finally, derivatives with long lipophilic alkyl chains could efficiently induce apoptosis. (C) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.07.011

文献信息

• A New Class of Naphthalimide-Based Antitumor Agents That Inhibit Topoisomerase II and Induce Lysosomal Membrane Permeabilization and Apoptosis
  作者：Zhuo Chen、Xin Liang、Huanying Zhang、Hua Xie、Jianwen Liu、Yufang Xu、Weiping Zhu、Yi Wang、Xin Wang、Shaoying Tan、Dong Kuang、Xuhong Qian

  DOI：10.1021/jm100025u

  日期：2010.3.25

  Based on the advantages of multitarget drugs for cancer treatment, a new class of naphthalimides was designed, synthesized, and proved to inhibit topoisomerase II (topo II), induced lysosomal membrane permeabilization (LMP), and ultimately caused apoptosis and cell death. The majority of compounds 7a-d and 8a-d potently inhibited the growth of the five tested cancer cell lines with IC(50) values ranging from 2 to 10 mu M and are more active than amonafide, a naphthahmide that was in phase III clinical trials. These compounds were tested for their interactions with DNA and their cell-free topo II inhibition activities, which demonstrated these compounds were weak DNA binders but modest topo II inhibitors. Furthermore, compounds 7b-d were found to notably induce LMP and exhibited better antiproliferative activity compared with their single-target analogues. All of the newly synthesized compounds were demonstrated to efficiently induce apoptosis via a mitochondrial pathway. Accordingly, a new paradigm was suggested for the design of novel multitarget anticancer drugs.
• Naphthalimides exhibit in vitro antiproliferative and antiangiogenic activities by inhibiting both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs)
  作者：Xin Wang、Zhuo Chen、Linjiang Tong、Shaoying Tan、Wei Zhou、Ting Peng、Kun Han、Jian Ding、Hua Xie、Yufang Xu

  DOI：10.1016/j.ejmech.2013.05.002

  日期：2013.7

  Novel naphthalimide derivatives were designed and synthesized to modulate both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs). Most target compounds exhibited effective and selective antiproliferative activities against three cancer cell lines by inhibiting topo II. The IC50 values ranged from 1.5 to 19.1 mu M. Moreover, compounds 8d and 12d moderately inhibited various angiogenesis-related RTKs, including FGFR1, VEGFR2 and PDGFR alpha. The representative compound 8d was then proved to possess antiangiogenic activity, which was evidenced by the inhibition of migration and tube formation activities of HMEC-1 cells. To our knowledge, it is the first time naphthalimides were identified as tyrosine kinases inhibitors (TKIs) besides their conventional cytotoxicity. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Novel metal complexes of naphthalimide–cyclam conjugates as potential multi-target receptor tyrosine kinase (RTK) inhibitors: Synthesis and biological evaluation
  作者：Shaoying Tan、Kun Han、Qiang Li、Linjiang Tong、Yiqi Yang、Zhuo Chen、Hua Xie、Jian Ding、Xuhong Qian、Yufang Xu

  DOI：10.1016/j.ejmech.2014.07.068

  日期：2014.10

  A novel series of metal complexes of naphthalimide-cyclam conjugates were synthesized and their in vitro antitumor activities were evaluated. The newly-synthesized compounds showed huge diversity of antiproliferative potency due to variety of metal ions and length of alkyl chains, among which the Zn(II) and Cr(III) complexes exhibited comparable antiproliferative activities with amonafide via multiple tyrosine kinase inhibition. Further research revealed that the representative compound 8a displayed broad-spectrum antiproliferative activity against 15 cancer cell lines with average IC50 value 10.18 +/- 3.25 mu M, and effective antiangiogenic activity on human microvascular endothelial cells (HMEC-1). In brief, metal complexes of naphthalimide-cyclam conjugates were firstly designed and synthesized as multi-target tyrosine kinase inhibitors and proved of their antitumor capacities. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Antiproliferative and apoptosis-inducing activities of novel naphthalimide–cyclam conjugates through dual topoisomerase (topo) I/II inhibition
  作者：Shaoying Tan、Deheng Sun、Jiankun Lyu、Xiao Sun、Fangshu Wu、Qiang Li、Yiqi Yang、Jianxu Liu、Xin Wang、Zhuo Chen、Honglin Li、Xuhong Qian、Yufang Xu

  DOI：10.1016/j.bmc.2015.07.011

  日期：2015.9

  A novel series of naphthalimide-cyclam conjugates were designed and synthesized. Among them, compounds 4c, 4d, 8c and 8d which bearing long lipophilic alkyl chains, displayed comparable or more potent cytotoxic activities against human tumor cell lines than amonafide. Furthermore, the four compounds were proved to possess strong inhibition against both topoisomerase I and II. The representative compound 8c exhibited moderate DNA intercalation activity. Molecular modeling studies identified the possible interaction of compound 8c with the molecular target by forming topoisomerase/DNA/drug ternary complex. Finally, derivatives with long lipophilic alkyl chains could efficiently induce apoptosis. (C) 2015 Published by Elsevier Ltd.