7-chloro-2-(4-chloro-phenyl)-quinoline-4-carboxylic acid | 6338-16-5

• 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: 7-chloro-2-(4-chloro-phenyl)-quinoline-4-carboxylic acid
• 英文别名: 7-Chlor-2-(4-chlor-phenyl)-chinolin-4-carbonsaeure；7-Chloro-2-(4-chlorophenyl)quinoline-4-carboxylic acid
• CAS: 6338-16-5
• 化学式: C₁₆H₉Cl₂NO₂
• 分子量: 318.159
• InChiKey: VZUQNWWKOLPWLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-chloro-2-(4-chloro-phenyl)-quinoline-4-carboxylic acid 、 N-甲基苄胺 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到N-benzyl-7-chloro-2-(4-chlorophenyl)-N-methylquinoline-4-carboxamide
  参考文献：
  名称：

  Discovery of novel tubulin inhibitors targeting the colchicine binding site via virtual screening, structural optimization and antitumor evaluation

  摘要：

  The colchicine binding site of tubulin is a promising target for discovering novel antitumor agents which exert the antiangiogenic effect and are not susceptible to multidrug resistance. For identifying novel tubulin inhibitors, structure-based virtual screening was applied to identify hit 9 which displayed moderate tubulin polymerization inhibition and broad-spectrum in vitro antitumor activity. Structural optimization was performed, and biological assay revealed analog E27 displayed the best antitumor activity with IC50 values ranging from 7.81 μM to 10.36 μM, and improved tubulin polymerization inhibitory activity (IC50 = 16.1 μM). It significantly inhibited cancer cell migration and invasion, induced cell apoptosis and arrested the cell cycle at G2/M phase. Moreover, the apoptotic effect of E27 is related to the increased ROS level, the decrease of MMP, and the abnormal expression of apoptosis-related proteins. Taken together, these results suggested E27 was a promising lead compound for discovering novel tubulin-targeted antitumor agents.

  DOI：

  10.1016/j.bioorg.2021.105486
• 作为产物：
  描述：

  6-氯靛红 、 对氯苯乙酮 在 水 、 potassium hydroxide 作用下， 反应 24.0h， 生成 7-chloro-2-(4-chloro-phenyl)-quinoline-4-carboxylic acid
  参考文献：
  名称：

  Discovery of novel tubulin inhibitors targeting the colchicine binding site via virtual screening, structural optimization and antitumor evaluation

  摘要：

  The colchicine binding site of tubulin is a promising target for discovering novel antitumor agents which exert the antiangiogenic effect and are not susceptible to multidrug resistance. For identifying novel tubulin inhibitors, structure-based virtual screening was applied to identify hit 9 which displayed moderate tubulin polymerization inhibition and broad-spectrum in vitro antitumor activity. Structural optimization was performed, and biological assay revealed analog E27 displayed the best antitumor activity with IC50 values ranging from 7.81 μM to 10.36 μM, and improved tubulin polymerization inhibitory activity (IC50 = 16.1 μM). It significantly inhibited cancer cell migration and invasion, induced cell apoptosis and arrested the cell cycle at G2/M phase. Moreover, the apoptotic effect of E27 is related to the increased ROS level, the decrease of MMP, and the abnormal expression of apoptosis-related proteins. Taken together, these results suggested E27 was a promising lead compound for discovering novel tubulin-targeted antitumor agents.

  DOI：

  10.1016/j.bioorg.2021.105486

文献信息

• Antimalarials. 7-Chloro-4-hydroxy- and 4,7-Dichloro-1-methylcarbostyrils¹
  作者：Robert E. Lutz、John F. Codington、Russell J. Rowlett、Adolf J. Deinet、Philip S. Bailey

  DOI：10.1021/ja01213a041

  日期：1946.9
• Quinoline derivatives having antimalarial properties
  申请人：US SEC WAR

  公开号：US02502264A1

  公开（公告）日：1950-03-28
• Discovery of novel tubulin inhibitors targeting the colchicine binding site via virtual screening, structural optimization and antitumor evaluation
  作者：Wei Liu、Hairui Jia、Minghao Guan、Minxuan Cui、Zhuxuan Lan、Youyou He、Zhongjie Guo、Ru Jiang、Guoqiang Dong、Shengzheng Wang

  DOI：10.1016/j.bioorg.2021.105486

  日期：2022.1

  The colchicine binding site of tubulin is a promising target for discovering novel antitumor agents which exert the antiangiogenic effect and are not susceptible to multidrug resistance. For identifying novel tubulin inhibitors, structure-based virtual screening was applied to identify hit 9 which displayed moderate tubulin polymerization inhibition and broad-spectrum in vitro antitumor activity. Structural optimization was performed, and biological assay revealed analog E27 displayed the best antitumor activity with IC50 values ranging from 7.81 μM to 10.36 μM, and improved tubulin polymerization inhibitory activity (IC50 = 16.1 μM). It significantly inhibited cancer cell migration and invasion, induced cell apoptosis and arrested the cell cycle at G2/M phase. Moreover, the apoptotic effect of E27 is related to the increased ROS level, the decrease of MMP, and the abnormal expression of apoptosis-related proteins. Taken together, these results suggested E27 was a promising lead compound for discovering novel tubulin-targeted antitumor agents.