(E)-N-phenethyl-2-(pyridin-2-ylmethylene)hydrazine-1-carbothioamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (E)-N-phenethyl-2-(pyridin-2-ylmethylene)hydrazine-1-carbothioamide
• 英文别名: 2-Formylpyridine N-(4)-phenylethylthiosemicarbazone；1-(2-phenylethyl)-3-[(E)-pyridin-2-ylmethylideneamino]thiourea
• 化学式: C₁₅H₁₆N₄S
• 分子量: 284.385
• InChiKey: BEOVDXWRLKDDOU-LDADJPATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-苯基乙基异硫代氰酸酯 在 hydrazine hydrate 、 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (E)-N-phenethyl-2-(pyridin-2-ylmethylene)hydrazine-1-carbothioamide
  参考文献：
  名称：

  含有吲哚片段作为有效和选择性抗癌剂的新型硫半脲类衍生物。

  摘要：

  高效，安全的抗癌药物的研发仍在促进人类健康。在本报告中，设计并合成了一系列新型的含吲哚片段的硫半碳环素衍生物。大多数化合物对PC3，MGC803和EC109细胞系均表现出优异的抗增殖活性，且IC50（0.14-12μM）低。特别地，化合物5j可以选择性地抑制三个测试的肿瘤细胞中的PC3细胞，IC50值为0.14μM，这可能归因于将吲哚片段引入TSC结构后的协同作用。同时，与3-AP和DPC相比，化合物5j在PC3细胞中对两种正常的WPMY-1和GES-1细胞系表现出更高的选择性。我们还发现5j可以有效抑制PC3细胞增殖，定植并诱导细胞凋亡。更重要的是，5j可能通过阻止EMT过程来显着抑制迁移和侵袭，但对细胞周期没有影响。总体而言，我们的研究结果表明，具有吲哚硫半脲的结构的5j可以用作进一步优化和开发的有用的抗癌药物。

  DOI：

  10.1016/j.ejmech.2019.111764

文献信息

• Novel thiosemicarbazone derivatives containing indole fragment as potent and selective anticancer agent
  作者：Zhangxu He、Hui Qiao、Feifei Yang、Wenjuan Zhou、Yunpeng Gong、Xinhui Zhang、Haojie Wang、Bing Zhao、Liying Ma、Hong-min Liu、Wen Zhao

  DOI：10.1016/j.ejmech.2019.111764

  日期：2019.12

  are still on the way to human health. In this report, a series of novel thiosemicarbazone derivatives containing indole fragment were designed and synthesized. Most compounds exhibited excellent antiproliferative activity against PC3, MGC803 and EC109 cell lines with low micromolar IC50 (0.14-12μM). Especially, compound 5j can selectively inhibit PC3 cells in three tested tumor cells with IC50 value of

  高效，安全的抗癌药物的研发仍在促进人类健康。在本报告中，设计并合成了一系列新型的含吲哚片段的硫半碳环素衍生物。大多数化合物对PC3，MGC803和EC109细胞系均表现出优异的抗增殖活性，且IC50（0.14-12μM）低。特别地，化合物5j可以选择性地抑制三个测试的肿瘤细胞中的PC3细胞，IC50值为0.14μM，这可能归因于将吲哚片段引入TSC结构后的协同作用。同时，与3-AP和DPC相比，化合物5j在PC3细胞中对两种正常的WPMY-1和GES-1细胞系表现出更高的选择性。我们还发现5j可以有效抑制PC3细胞增殖，定植并诱导细胞凋亡。更重要的是，5j可能通过阻止EMT过程来显着抑制迁移和侵袭，但对细胞周期没有影响。总体而言，我们的研究结果表明，具有吲哚硫半脲的结构的5j可以用作进一步优化和开发的有用的抗癌药物。
• Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents
  作者：Xin-Hui Zhang、Bo-Wang、Yuan-Yuan Tao、Qin Ma、Hao-Jie Wang、Zhang-Xu He、Hui-Pan Wu、Yi-Han Li、Bing Zhao、Li-Ying Ma、Hong-Min Liu

  DOI：10.1016/j.ejmech.2020.112349

  日期：2020.8

  In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC50 value of 0.031 mu M, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial-mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer. (C) 2020 Elsevier Masson SAS. All rights reserved.