(7-methyl-2-oxo-2H-chromen-4-yl)methyl pyrrolidine-1-carbodithioate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: (7-methyl-2-oxo-2H-chromen-4-yl)methyl pyrrolidine-1-carbodithioate
• 英文别名: (7-Methyl-2-oxochromen-4-yl)methyl pyrrolidine-1-carbodithioate
• 化学式: C₁₆H₁₇NO₂S₂
• 分子量: 319.448
• InChiKey: PLQNYHDYLYNQJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  86.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  间甲酚 在 硫酸 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 25.83h， 生成 (7-methyl-2-oxo-2H-chromen-4-yl)methyl pyrrolidine-1-carbodithioate
  参考文献：
  名称：

  Novel synthetic coumarins that targets NF-κB in Hepatocellular carcinoma

  摘要：

  Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor worldwide, and is the third most common cause of cancer related death. Constitutive activation of NF-kappa B is the underlying mechanism behind tumorigenesis and this protein regulates the expression of genes involved in proliferation, survival, drug resistance, angiogenesis and metastasis. The design of inhibitors which suppress NF-kappa B activation is therefore of great therapeutic importance in the treatment of HCC. In this study, we investigated the effect of newly synthesized coumarin derivatives against HCC cells, and identified (7-Carbethoxyamino-2-oxo-2H-chromen-4-yl)methylpyrrolidine-1 carbodithioate (CPP) as lead compound. Further, we evaluated the effect of CPP on the DNA binding ability of NF-kappa B, CXCL12-induced cell migration and invasion, and the regulated gene products in HCC cells. We found that CPP induced cytotoxicity in three HCC cells in a time and dose dependent manner, and suppressed the DNA binding ability of NF-kappa B. CPP significantly decreased the CXCL12-induced cell migration and invasion. More evidently, CPP inhibits the expression of NF-kappa B targeted genes such as cyclin D1, Bcl-2, survivin, MMP12 and C-Myc. Furthermore, the molecular docking analysis suggested that CPP interacts with the p50 binding domain of the p65 sub-unit, scoring best among the 26 docked coumarin derivatives of this study. Thus, we are reporting CPP as a potent inhibitor of the pro-inflammatory pathway in Hepatocellular carcinoma. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.065

文献信息

• Novel synthetic coumarins that targets NF-κB in Hepatocellular carcinoma
  作者：Mahabaleshwaraiah Neelgundmath、Koragere Rajashekar Dinesh、Chakrabhavi Dhananjaya Mohan、Feng Li、Xiaoyun Dai、Kodappully Sivaraman Siveen、Shardul Paricharak、Daniel J. Mason、Julian E. Fuchs、Gautam Sethi、Andreas Bender、Kanchugarakoppal S. Rangappa、Obelannavar Kotresh、Basappa

  DOI：10.1016/j.bmcl.2014.12.065

  日期：2015.2

  Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor worldwide, and is the third most common cause of cancer related death. Constitutive activation of NF-kappa B is the underlying mechanism behind tumorigenesis and this protein regulates the expression of genes involved in proliferation, survival, drug resistance, angiogenesis and metastasis. The design of inhibitors which suppress NF-kappa B activation is therefore of great therapeutic importance in the treatment of HCC. In this study, we investigated the effect of newly synthesized coumarin derivatives against HCC cells, and identified (7-Carbethoxyamino-2-oxo-2H-chromen-4-yl)methylpyrrolidine-1 carbodithioate (CPP) as lead compound. Further, we evaluated the effect of CPP on the DNA binding ability of NF-kappa B, CXCL12-induced cell migration and invasion, and the regulated gene products in HCC cells. We found that CPP induced cytotoxicity in three HCC cells in a time and dose dependent manner, and suppressed the DNA binding ability of NF-kappa B. CPP significantly decreased the CXCL12-induced cell migration and invasion. More evidently, CPP inhibits the expression of NF-kappa B targeted genes such as cyclin D1, Bcl-2, survivin, MMP12 and C-Myc. Furthermore, the molecular docking analysis suggested that CPP interacts with the p50 binding domain of the p65 sub-unit, scoring best among the 26 docked coumarin derivatives of this study. Thus, we are reporting CPP as a potent inhibitor of the pro-inflammatory pathway in Hepatocellular carcinoma. (C) 2014 Elsevier Ltd. All rights reserved.