4-(3,4-dichlorophenyl)piperazine-1-carbothiohydrazide | 1435909-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(3,4-dichlorophenyl)piperazine-1-carbothiohydrazide
• 英文别名: 4-(3,4-Dichlorophenyl)piperazine-1-carbothiohydrazide
• CAS: 1435909-42-4
• 化学式: C₁₁H₁₄Cl₂N₄S
• 分子量: 305.231
• InChiKey: NPYDCAVSHXSCMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  76.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3,4-dichlorophenyl)piperazine-1-carbothiohydrazide 、 香草醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 0.33h， 以64%的产率得到4-(3,4-dichlorophenyl)-N'-[(4-hydroxy-3-methoxyphenyl)methylidene]piperazine-1-carbothiohydrazide
  参考文献：
  名称：

  Impact of thiosemicarbazones on the accumulation of PpIX and the expression of the associated genes

  摘要：

  Thiosemicarbazone derivatives are known for their broad biological activity including their antitumor potency. The aim of the current study was to examine the effect of a novel series of non-toxic iron chelators on the accumulation of protoporphyrin IX after external 5-aminolevulonic acid administration. From this series we selected one the most promising derivative which causes a pronounced increase in the concentration of protoporphyrin IX. The increase of the photosensitizer concentration is necessary for the trigger the efficient therapeutic effect of the photodynamic reaction. For selected compound 2 we performed an examination of a panel of the genes that are involved in the heme biosynthesis and degradation. Results indicated the crucial roles of ferrochelatase and heme oxygenase in the described processes. Surprisingly, there was a strict dependence on the type of the tested cell line. A decrease in the expression of the two aforementioned enzymes after incubation with compound 2 and 5-aminolevulonic acid is a commonly known fact and we detected this trend for the MCF-7 and HCT 116 cell lines. However, we noticed the upregulation of the tested targets for the Hs683 cells. These unconventional results prompted us to do a more in-depth analysis of the described processes. In conclusion, we found that compound 2 is a novel, highly effective booster of photodynamic therapy that has prospective applications.

  DOI：

  10.1016/j.jphotobiol.2019.111585
• 作为产物：
  描述：

  1-(3,4-二氯苯基)哌嗪 在 一水合肼 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 生成 4-(3,4-dichlorophenyl)piperazine-1-carbothiohydrazide
  参考文献：
  名称：

  Anticancer activity of the thiosemicarbazones that are based on di-2-pyridine ketone and quinoline moiety

  摘要：

  Thiosemicarbazones (TSC) are a subclass of iron-chelating agents that are believed to have an anticancer activity. The high potential for the application of this compound class can be illustrated by a fact that three TSC have entered clinical trials. The ability to chelate metal ions results in several biochemical changes in the cellular metabolism and growth. An important factor that determines the antitumor activity of TSC is a level of iron regulatory proteins and the antioxidant potential that is specific for each type of cancer cell. However, despite the increasing interest in TSC, their mechanism of anticancer activity is still unclear. For a more effective and rational design, it is crucial to determine and describe the abovementioned issues. In this report, we describe a series of new TSC that are designed on the four main structural scaffolds. The anticancer activity of these compounds was evaluated against a panel of cancer cell lines including colon and breast cancers and gliomas. Special attention was paid to the metal dependent proteins. The impact of the tested TSC on the cell cycle and redox homeostasis was also determined. These results confirm a p53-independent mechanism of apoptosis. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.027

文献信息

• Synthesis and antiproliferative evaluation of piperazine-1-carbothiohydrazide derivatives of indolin-2-one
  作者：Hui-Hui Lin、Wei-Yao Wu、Sheng-Li Cao、Ji Liao、Li Ma、Man Gao、Zhong-Feng Li、Xingzhi Xu

  DOI：10.1016/j.bmcl.2013.03.099

  日期：2013.6

  By varying the substituents (R-1) at the indolin-2-one scaffold, a series of indolin-2-one derivatives bearing 4-phenylpiperazine-1-carbothiohydrazide moiety at the C3-position were synthesized and evaluated for their antiproliferative activity against three human cancer cell lines. We further selected the 5-chloroindolin-2-one moiety for the extension to another series of compounds by varying the substituents (R-2) at the phenyl group connected with the piperazine ring. Among all the compounds synthesized, 6d and 6l were most potent with IC50 values of 3.59 and 5.58 mu M, respectively against A549 lung cancer cells, while 5f and 6l possessed IC50 values of 3.49 and 4.57 mu M, respectively against HCT-116 colon cancer cells which were comparable to that of Sunitinib, an indolin-2-one derivative in cancer therapy. (C) 2013 Elsevier Ltd. All rights reserved.
• Impact of thiosemicarbazones on the accumulation of PpIX and the expression of the associated genes
  作者：Robert Gawecki、Katarzyna Malarz、Marta Rejmund、Jaroslaw Polanski、Anna Mrozek-Wilczkiewicz

  DOI：10.1016/j.jphotobiol.2019.111585

  日期：2019.10

  Thiosemicarbazone derivatives are known for their broad biological activity including their antitumor potency. The aim of the current study was to examine the effect of a novel series of non-toxic iron chelators on the accumulation of protoporphyrin IX after external 5-aminolevulonic acid administration. From this series we selected one the most promising derivative which causes a pronounced increase in the concentration of protoporphyrin IX. The increase of the photosensitizer concentration is necessary for the trigger the efficient therapeutic effect of the photodynamic reaction. For selected compound 2 we performed an examination of a panel of the genes that are involved in the heme biosynthesis and degradation. Results indicated the crucial roles of ferrochelatase and heme oxygenase in the described processes. Surprisingly, there was a strict dependence on the type of the tested cell line. A decrease in the expression of the two aforementioned enzymes after incubation with compound 2 and 5-aminolevulonic acid is a commonly known fact and we detected this trend for the MCF-7 and HCT 116 cell lines. However, we noticed the upregulation of the tested targets for the Hs683 cells. These unconventional results prompted us to do a more in-depth analysis of the described processes. In conclusion, we found that compound 2 is a novel, highly effective booster of photodynamic therapy that has prospective applications.
• Anticancer activity of the thiosemicarbazones that are based on di-2-pyridine ketone and quinoline moiety
  作者：Anna Mrozek-Wilczkiewicz、Katarzyna Malarz、Marta Rejmund、Jaroslaw Polanski、Robert Musiol

  DOI：10.1016/j.ejmech.2019.03.027

  日期：2019.6

  Thiosemicarbazones (TSC) are a subclass of iron-chelating agents that are believed to have an anticancer activity. The high potential for the application of this compound class can be illustrated by a fact that three TSC have entered clinical trials. The ability to chelate metal ions results in several biochemical changes in the cellular metabolism and growth. An important factor that determines the antitumor activity of TSC is a level of iron regulatory proteins and the antioxidant potential that is specific for each type of cancer cell. However, despite the increasing interest in TSC, their mechanism of anticancer activity is still unclear. For a more effective and rational design, it is crucial to determine and describe the abovementioned issues. In this report, we describe a series of new TSC that are designed on the four main structural scaffolds. The anticancer activity of these compounds was evaluated against a panel of cancer cell lines including colon and breast cancers and gliomas. Special attention was paid to the metal dependent proteins. The impact of the tested TSC on the cell cycle and redox homeostasis was also determined. These results confirm a p53-independent mechanism of apoptosis. (C) 2019 Elsevier Masson SAS. All rights reserved.