10-chloro-8-methyl-11H-indeno[1,2-b]quinoline | 97738-14-2

• 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: 10-chloro-8-methyl-11H-indeno[1,2-b]quinoline
• 英文别名: 10-chloro-8-methyl-11H-indeno[1,2-b]quinoline；4-Chlor-6-methyl-1',2':2,3-indeno-chinolin
• CAS: 97738-14-2
• 化学式: C₁₇H₁₂ClN
• 分子量: 265.742
• InChiKey: IKRGINSPLQDJPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.77
• 重原子数：
  19.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  12.89
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  N-(3-氨丙基)吗啉 、 10-chloro-8-methyl-11H-indeno[1,2-b]quinoline 以 乙二醇 为溶剂， 以45%的产率得到8-methyl-11H-indeno[1,2-b]quinolin-10-yl-(3-morpholinopropylamine)
  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
• 作为产物：
  描述：

  2-氨基-5-甲基苯甲酸 在 三氯氧磷 作用下， 以 neat (no solvent) 为溶剂， 生成 10-chloro-8-methyl-11H-indeno[1,2-b]quinoline
  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