(E)-3-(1H-indol-4-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(1H-indol-4-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 化学式: C₂₀H₁₉NO₄
• 分子量: 337.375
• InChiKey: NRWULFAUHWILHE-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  60.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(1H-indol-4-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 在 水 、 potassium carbonate 、 potassium iodide 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (E)-3-(4-(3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-1H-indol-1-yl)propanoic acid
  参考文献：
  名称：

  源自吲哚查耳酮和喜树碱的新型 GSH 响应性前药可触发结肠癌的细胞凋亡和自噬

  摘要：

   [显示省略]

  DOI：

  10.1016/j.bioorg.2023.107056
• 作为产物：
  描述：

  4-吲哚甲醛 、 3',4',5'-三甲氧基苯乙酮 在 哌啶 作用下， 以 乙醇 为溶剂， 以55 %的产率得到(E)-3-(1H-indol-4-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  源自吲哚查耳酮和喜树碱的新型 GSH 响应性前药可触发结肠癌的细胞凋亡和自噬

  摘要：

   [显示省略]

  DOI：

  10.1016/j.bioorg.2023.107056

文献信息

• Novel Indole–Chalcone Derivative-Ligated Platinum(IV) Prodrugs Attenuate Cisplatin Resistance in Lung Cancer through ROS/ER Stress and Mitochondrial Dysfunction
  作者：Zhikun Liu、Meng Wang、Rizhen Huang、Tianhui Hu、Yi Jing、Xiaochao Huang、Weiwei Hu、Guoxiu Cao、Hengshan Wang

  DOI：10.1021/acs.jmedchem.2c02036

  日期：——

  against the tested cells but showed lower cytotoxicity toward human normal lung cells. Detailed mechanisms demonstrated that 17a significantly enhanced intracellular accumulation, induced DNA damage, and inhibited migration in A549/CDDP cells. Furthermore, 17a efficiently disturbed the tubulin–microtubule system, initiated reactive oxygen species (ROS)-mediated endoplasmic reticulum stress, and activated

  通过将生物活性药效团整合到一个实体中开发多功能铂（IV）前药是改善铂（II）药物缺陷的有吸引力的策略。在此，合成了一系列吲哚-查耳酮衍生物连接的铂 (IV) 配合物并评估了它们的抗癌活性。其中，与顺铂 (CDDP) 相比，最佳复合物17a对受试细胞具有更高的活性，但对人类正常肺细胞的细胞毒性较低。详细的机制表明，17a显着增强细胞内积累，诱导 DNA 损伤，并抑制 A549/CDDP 细胞的迁移。此外，17a有效地扰乱微管蛋白-微管系统，启动活性氧 (ROS) 介导的内质网应激，并激活线粒体依赖性细胞凋亡信号通路。此外，17a在抑制 A549 / CDDP 异种移植物中的癌症生长方面优于游离药物或其组合，而不会引起明显的副作用。16a和 CDDP的物理混合物与17a几乎相同，但显示出明显的系统性副作用。总之，我们的研究可能为 CDDP 耐药提供有效的治疗方案。
• Synthesis, Evaluation, and Mechanism Study of Novel Indole-Chalcone Derivatives Exerting Effective Antitumor Activity Through Microtubule Destabilization in Vitro and in Vivo
  作者：Jun Yan、Jie Chen、Shun Zhang、Jinhui Hu、Ling Huang、Xingshu Li

  DOI：10.1021/acs.jmedchem.6b00021

  日期：2016.6.9

  Twenty-nine novel indole-chalcone derivatives were synthesized and evaluated for antiproliferative activity. Among them, 14k exhibited most potent activity, with IC50 values of 3-9 nM against six cancer cells, which displayed a 3.8-8.7-fold increase in activity when compare with compound 2. Further investigation revealed 14k was a novel tubulin polymerization inhibitor binding to the colchicine site. Its low cytotoxicity toward normal human cells and nearly equally potent activity against drug resistant cells revealed the possibility for cancer therapy. Cellular mechanism studies elucidated 14k arrests cell cycle at G(2)/M phase and induces apoptosis along with the decrease of mitochondrial membrane potential. Furthermore, good metabolic stability of 14k was observed in mouse liver microsomes. Importantly, 14k and its phosphate salt 14k-P inhibited tumor growth in xenograft models in vivo without apparent toxicity, which was better than the reference compound CA-4P and 2. In summary, 14k deserves consideration for cancer therapy.
• Novel indole–chalcone platinum(IV) complexes as tubulin polymerization inhibitors to overcome oxaliplatin resistance in colorectal cancer
  作者：Xinguang Cao、Rui Li、Hui Wang、Changqing Guo、Saiqi Wang、Xiaobing Chen、Ruihua Zhao

  DOI：10.1016/j.molstruc.2022.134169

  日期：2023.1