(E)-3-(4-methoxy-1-methyl-1H-indol-3-yl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (E)-3-(4-methoxy-1-methyl-1H-indol-3-yl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)prop-2-en-1-one
• 英文别名: (E)-1-(5-methoxy-2,2-dimethylchromen-8-yl)-3-(4-methoxy-1-methylindol-3-yl)prop-2-en-1-one
• 化学式: C₂₅H₂₅NO₄
• 分子量: 403.478
• InChiKey: FXZVUJVQFCKADY-PKNBQFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-甲氧基吲哚 在 哌啶 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 48.0h， 生成 (E)-3-(4-methoxy-1-methyl-1H-indol-3-yl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)prop-2-en-1-one
  参考文献：
  名称：

  Synthesis, Evaluation, and Mechanism Study of Novel Indole-Chalcone Derivatives Exerting Effective Antitumor Activity Through Microtubule Destabilization in Vitro and in Vivo

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.6b00021

文献信息

• 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.