3-[1-(6-methoxynaphtalen-2-yl)ethyl]-6-(4-trifluoromethoxyphenyl)-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[1-(6-methoxynaphtalen-2-yl)ethyl]-6-(4-trifluoromethoxyphenyl)-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine
• 英文别名: 3-[1-(6-methoxynaphthalen-2-yl)ethyl]-6-[4-(trifluoromethoxy)phenyl]-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
• 化学式: C₂₄H₁₉F₃N₄O₂S
• 分子量: 484.502
• InChiKey: NBWAUXFAVGUGOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  86.8
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(6-甲氧基-2-萘基)丙酸 以 乙醇 为溶剂， 反应 1.0h， 生成 3-[1-(6-methoxynaphtalen-2-yl)ethyl]-6-(4-trifluoromethoxyphenyl)-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine
  参考文献：
  名称：

  Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins

  摘要：

  Newly designed triazolothiadiazines incorporating with structural motifs of nonsteroidal analgesic anti-inflammatory drugs were synthesized and screened for their bioactivity against epithelial cancer cells. Compounds with bioactivities less then similar to 5 mu M (IC50) were further analyzed and showed to induce apoptotic cell death and SubG(1) cell cycle arrest in liver cancer cells. Among this group, two compounds (1g and 1h) were then studied to identify the mechanism of action. These molecules triggered oxidative stress induced apoptosis through ASK-1 protein activation and Akt protein inhibition as demonstrated by downstream targets such as GSK3 beta, beta-catenin and cyclin D1. QSAR and molecular docking models provide insight into the mechanism of inhibition and indicate the optimal direction of future synthetic efforts. Furthermore, molecular docking results were confirmed with in vitro COX bioactivity studies. This study demonstrates that the novel triazolothiadiazine derivatives are promising drug candidates for epithelial cancers, especially liver cancer. (c) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2016.01.013

文献信息

• Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins
  作者：Peri S. Aytaç、Irem Durmaz、Douglas R. Houston、Rengül Çetin-Atalay、Birsen Tozkoparan

  DOI：10.1016/j.bmc.2016.01.013

  日期：2016.2

  Newly designed triazolothiadiazines incorporating with structural motifs of nonsteroidal analgesic anti-inflammatory drugs were synthesized and screened for their bioactivity against epithelial cancer cells. Compounds with bioactivities less then similar to 5 mu M (IC50) were further analyzed and showed to induce apoptotic cell death and SubG(1) cell cycle arrest in liver cancer cells. Among this group, two compounds (1g and 1h) were then studied to identify the mechanism of action. These molecules triggered oxidative stress induced apoptosis through ASK-1 protein activation and Akt protein inhibition as demonstrated by downstream targets such as GSK3 beta, beta-catenin and cyclin D1. QSAR and molecular docking models provide insight into the mechanism of inhibition and indicate the optimal direction of future synthetic efforts. Furthermore, molecular docking results were confirmed with in vitro COX bioactivity studies. This study demonstrates that the novel triazolothiadiazine derivatives are promising drug candidates for epithelial cancers, especially liver cancer. (c) 2016 Published by Elsevier Ltd.