(E)-2-((1-phenyl-5-(4-sulfamoylphenyl)-1H-1,2,4-triazol-3-yl)thio)ethyl 3-(3,4-dihydroxyphenyl)acrylate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-2-((1-phenyl-5-(4-sulfamoylphenyl)-1H-1,2,4-triazol-3-yl)thio)ethyl 3-(3,4-dihydroxyphenyl)acrylate
• 英文别名: (E)-3-(3,4-dihydroxyphenyl)acrylic acid 2-[1-phenyl-5-(4-sulfamoylphenyl)-1H-1,2,4-triazol-3-yl]thioethyl ester；2-[[1-phenyl-5-(4-sulfamoylphenyl)-1,2,4-triazol-3-yl]sulfanyl]ethyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
• 化学式: C₂₅H₂₂N₄O₆S₂
• 分子量: 538.605
• InChiKey: AOJLCKAGSOKLCP-NTUHNPAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  191
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  苯胺基硫脲 在 sodium methylate 、 potassium carbonate 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 28.0h， 生成 (E)-2-((1-phenyl-5-(4-sulfamoylphenyl)-1H-1,2,4-triazol-3-yl)thio)ethyl 3-(3,4-dihydroxyphenyl)acrylate
  参考文献：
  名称：

  Discovery of novel hybrids of diaryl-1,2,4-triazoles and caffeic acid as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for cancer therapy

  摘要：

  Inflammation plays a key role in cancer initiation and propagation. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two important enzymes in inflammatory responses are up-regulated in various tumor types. Dual inhibition of COX-2 and 5-LOX constitutes a rational concept for the design of more efficacious anti-tumor agents with an improved safety profile. We have previously reported a series of diaryl-1,2,4-triazole derivatives as selective COX-2 inhibitors. Herein, we hybridized the diaryl-1,2,4triazoles with caffeic acid (CA) which was reported to display 5-LOX inhibitory and anti-tumor activities, affording a novel class of COX-2/5-LOX dual inhibitors as anti-tumor drug candidates. Most of these compounds exhibited potent COX-2/5-LOX inhibitory and antiproliferative activities in vitro. And the most potent compound 22b could significantly inhibit tumor growth in vivo. Furthermore, mechanistic investigation showed that the representative compound 15c blocked cell cycle in G2 phase and induced apoptosis in human non-small cell lung cancer A549 cells in a dose-dependent manner. Our preliminary investigation results would provide new clues for the cancer theatment with COX-2/5-LOX dual inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.013

文献信息

• Discovery of novel hybrids of diaryl-1,2,4-triazoles and caffeic acid as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for cancer therapy
  作者：Hao Cai、Xiaojing Huang、Shengtao Xu、Hao Shen、Pengfei Zhang、Yue Huang、Jieyun Jiang、Yijun Sun、Bo Jiang、Xiaoming Wu、Hequan Yao、Jingyi Xu

  DOI：10.1016/j.ejmech.2015.11.013

  日期：2016.1

  Inflammation plays a key role in cancer initiation and propagation. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two important enzymes in inflammatory responses are up-regulated in various tumor types. Dual inhibition of COX-2 and 5-LOX constitutes a rational concept for the design of more efficacious anti-tumor agents with an improved safety profile. We have previously reported a series of diaryl-1,2,4-triazole derivatives as selective COX-2 inhibitors. Herein, we hybridized the diaryl-1,2,4triazoles with caffeic acid (CA) which was reported to display 5-LOX inhibitory and anti-tumor activities, affording a novel class of COX-2/5-LOX dual inhibitors as anti-tumor drug candidates. Most of these compounds exhibited potent COX-2/5-LOX inhibitory and antiproliferative activities in vitro. And the most potent compound 22b could significantly inhibit tumor growth in vivo. Furthermore, mechanistic investigation showed that the representative compound 15c blocked cell cycle in G2 phase and induced apoptosis in human non-small cell lung cancer A549 cells in a dose-dependent manner. Our preliminary investigation results would provide new clues for the cancer theatment with COX-2/5-LOX dual inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.