1-propionyl-3,5-bis((E)-3,4,5-trimethoxybenzylidene)piperidin-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-propionyl-3,5-bis((E)-3,4,5-trimethoxybenzylidene)piperidin-4-one
• 英文别名: (3E,5E)-1-propanoyl-3,5-bis[(3,4,5-trimethoxyphenyl)methylidene]piperidin-4-one
• 化学式: C₂₈H₃₃NO₈
• 分子量: 511.572
• InChiKey: OLCACFVHKWHSAB-LQGKIZFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 在 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 mineral oil 为溶剂， 反应 12.5h， 生成 1-propionyl-3,5-bis((E)-3,4,5-trimethoxybenzylidene)piperidin-4-one
  参考文献：
  名称：

  Design, synthesis, anti-lung cancer activity, and chemosensitization of tumor-selective MCACs based on ROS-mediated JNK pathway activation and NF-κB pathway inhibition

  摘要：

  EF24 and F35 both were effective monocarbonyl curcumin analogues (MCACs) with excellent anti-tumor activity, however, drug defect such as toxicity may limit their further development. To get anti-lung cancer drugs with high efficiency, low toxicity and chemosensitization, a series of analogues based on EF24 and F35 were designed and synthesized. A number of compounds were found to exhibit cytotoxic activities selectively towards lung cancer cells compared to normal cells. Among these compounds, 5B was considered as an optimal anti-tumor agent for lung cancer cells with IC50 values ranging from 1.0 to 1.7 mu M, selectivity index (SI, as a logarithm of a ratio of IC50 value for normal and cancer cells) were all above 1.1, while the SI of EF24 and F35 were less than 0.8. Consistent with selectivity in vitro, 5B was observed to show lower toxicity in acute toxicity experiment than EF24 and F35 respectively. Further, 5B was found to exert anti-tumor effects through ROS-mediated activation of JNK pathway and inhibition of NF-kappa B pathway. 5B could significantly enhance the sensitivity of A549 cells to cisplatin or 5-Fu. These findings suggested that 5B was an effective and less toxic MCAC and provided a promising candidate for anti-tumor drugs. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.051