2-(3-bromopropyl)-6-(dodecylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione | 1207670-59-4

• 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: 2-(3-bromopropyl)-6-(dodecylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione
• 英文别名: 2-(3-Bromopropyl)-6-(dodecylamino)benzo[de]isoquinoline-1,3-dione
• CAS: 1207670-59-4
• 化学式: C₂₇H₃₇BrN₂O₂
• 分子量: 501.507
• InChiKey: UEGYFRRIHVENJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  32
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4,8,11-四氮杂环十四烷 、 2-(3-bromopropyl)-6-(dodecylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione 以 氯仿 为溶剂， 反应 72.0h， 以58%的产率得到2-(3-(1,4,8,11-tetraazacyclotetradecan-1-yl)propyl)-6-(dodecylamino)-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：

  6-bromo-2-(3-hydroxypropyl)-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 乙二醇甲醚 为溶剂， 生成 2-(3-bromopropyl)-6-(dodecylamino)-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.
• 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.