N'-11H-indeno[1,2-b]quinolin-10-yl-(N,N-dimethyl-1,3-diaminopropane) | 119971-32-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N'-11H-indeno[1,2-b]quinolin-10-yl-(N,N-dimethyl-1,3-diaminopropane)
• 英文别名: N¹-(11H-indeno[1,2-b]quinolin-10-yl)-N³,N³-dimethylpropane-1,3-diamine；N-(11H-indeno[1,2-b]quinolin-10-yl)-N',N'-dimethylpropane-1,3-diamine
• CAS: 119971-32-3
• 化学式: C₂₁H₂₃N₃
• 分子量: 317.434
• InChiKey: QGHWAMRAQGPRNP-UHFFFAOYSA-N

物化性质

• 熔点：
  81-83 °C
• 沸点：
  518.4±50.0 °C(Predicted)
• 密度：
  1.182±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5H-indeno[1,2-b]quinolin-10(11H)-one 在 三氯氧磷 作用下， 以 乙二醇 为溶剂， 生成 N'-11H-indeno[1,2-b]quinolin-10-yl-(N,N-dimethyl-1,3-diaminopropane)
  参考文献：
  名称：

  Cryptolepine and aromathecin based mimics as potent G-quadruplex-binding, DNA-cleavage and anticancer agents: Design, synthesis and DNA targeting-induced apoptosis

  摘要：

  Thirty Cryptolepine and Aromathecin based mimics were designed and synthesized. Their cytotoxicity was evaluated in four human cancer cell lines (HepG-2, T24, NCI-H460 and MGC-803) and one normal human cell line (HL-7702). Most compounds exhibited potent anticancer activity with IC50 values from 0.31 to 11.97 mu M. 8-Fluoro-10-(N-3-dimethylaminopropyl)amino-11H-indeno[1,2-b]quinoline (5b) was identified as the most promising candidate in view of its anticancer activity. Molecular mechanism studies suggested that 5b not only could strongly bind to G-quadruplex, but intercalate into supercoil DNA and resulted in significant DNA double-strand break as well. Furthermore, 5b caused cell cycle arrest at S/G2 phase and induced apoptosis. After treatment with 5b, pro-apoptotic proteins Bak, Bax and Bim were up-regulated, anti-apoptotic proteins Bcl-2 and Bcl-xL were down-regulated, and the effector caspase-3/9 was activated to initiate apoptosis. The anticancer activity of 5b was finally validated in a MGC-803 xenograft tumor model with tumor growth inhibition (TGI) up to 53.2%, while displaying no obvious toxicity. Taken together, these results suggest that 5b may be a potential candidate of cytotoxic antineoplastic drugs for cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.072

文献信息

• Synthesis and antitumor activity of fused tetracyclic quinoline derivatives. 1
  作者：Masatoshi Yamato、Yasuo Takeuchi、Kuniko Hashigaki、Yuji Ikeda、Ming Rong Chang、Kyoko Takeuchi、Mayumi Matsushima、Takashi Tsuruo、Tazuko Tashiro

  DOI：10.1021/jm00126a025

  日期：1989.6

  Several fused tri- and tetracyclic quinolines (I and II) with [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino or [3-(N,N-dimethylamino)propyl]amino side chains were prepared, and their DNA intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. Some compounds having both intercalative ability and

  制备了几个带有[2-甲氧基-4-[（甲基磺酰基）氨基]苯基]氨基或[3-（N，N-二甲基氨基）丙基]氨基侧链的稠合三环和四环喹啉（I和II），研究了DNA插入特性，KB细胞毒性，抗肿瘤活性（P388白血病）以及诱导拓扑异构酶II依赖性DNA裂解的能力。发现一些同时具有嵌入能力和KB细胞毒性的化合物在体内是无活性的。但是，在体内诱导拓扑异构酶II依赖性DNA切割的能力与抗肿瘤活性之间存在正相关。茚并（13a），苯并呋喃（21a）和苯并噻吩并（22a）喹啉衍生物在体外和体内均表现出与m-AMSA相当的抗肿瘤活性。它们还插入DNA并诱导拓扑异构酶II依赖性DNA切割。
• YAMATO, MASATOSHI;TAKEUCHI, YASUO;HISHIGAKI, KUNIKO;IKEDA, YUJI;MING-RONG+, J. MED. CHEM., 32,(1989) N, C. 1295-1300
  作者：YAMATO, MASATOSHI、TAKEUCHI, YASUO、HISHIGAKI, KUNIKO、IKEDA, YUJI、MING-RONG+

  DOI：——

  日期：——
• Cryptolepine and aromathecin based mimics as potent G-quadruplex-binding, DNA-cleavage and anticancer agents: Design, synthesis and DNA targeting-induced apoptosis
  作者：Jing-Mei Yuan、Kai Wei、Guo-Hai Zhang、Nan-Ying Chen、Xin-Wei Wei、Cheng-Xue Pan、Dong-Liang Mo、Gui-Fa Su

  DOI：10.1016/j.ejmech.2019.02.072

  日期：2019.5

  Thirty Cryptolepine and Aromathecin based mimics were designed and synthesized. Their cytotoxicity was evaluated in four human cancer cell lines (HepG-2, T24, NCI-H460 and MGC-803) and one normal human cell line (HL-7702). Most compounds exhibited potent anticancer activity with IC50 values from 0.31 to 11.97 mu M. 8-Fluoro-10-(N-3-dimethylaminopropyl)amino-11H-indeno[1,2-b]quinoline (5b) was identified as the most promising candidate in view of its anticancer activity. Molecular mechanism studies suggested that 5b not only could strongly bind to G-quadruplex, but intercalate into supercoil DNA and resulted in significant DNA double-strand break as well. Furthermore, 5b caused cell cycle arrest at S/G2 phase and induced apoptosis. After treatment with 5b, pro-apoptotic proteins Bak, Bax and Bim were up-regulated, anti-apoptotic proteins Bcl-2 and Bcl-xL were down-regulated, and the effector caspase-3/9 was activated to initiate apoptosis. The anticancer activity of 5b was finally validated in a MGC-803 xenograft tumor model with tumor growth inhibition (TGI) up to 53.2%, while displaying no obvious toxicity. Taken together, these results suggest that 5b may be a potential candidate of cytotoxic antineoplastic drugs for cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.