6-bitro-2-oxo-N'-(2-oxoindolin-3-ylidene)-2H-chromene-3-carbohydrazide | 326884-83-7

• 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: 6-bitro-2-oxo-N'-(2-oxoindolin-3-ylidene)-2H-chromene-3-carbohydrazide
• 英文别名: 6-nitro-2-oxo-N'-(2-oxoindol-3-yl)chromene-3-carbohydrazide
• CAS: 326884-83-7
• 化学式: C₁₈H₁₀N₄O₆
• 分子量: 378.301
• InChiKey: LTYNAMFQXYMQEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.79
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  143.91
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  靛红 在 哌啶 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 6.5h， 生成 6-bitro-2-oxo-N'-(2-oxoindolin-3-ylidene)-2H-chromene-3-carbohydrazide
  参考文献：
  名称：

  Anticancer activity of new coumarin substituted hydrazide–hydrazone derivatives

  摘要：

  Drug resistance is a major impediment for cancer treatment, to overcome it we designed and synthesized sixteen coumarins bearing hydrazide-hydrazone moiety and evaluated them against human drug-resistant pancreatic carcinoma (Panc-1) cells and drug-sensitive (hepatic carcinoma; Hep-G2 and leukemia; CCRF) cell lines in vitro. The 6-brominated coumarin hydrazide-hydrazone derivatives (BCHHD) 7c, 8c and 10c were more potent than doxorubicin (DOX) against resistant Panc-1 cells. BCHHD 7c showed significant cytotoxicity against all tested cells (IC50: 3.60-6.50 mu M) on comparison with all other coumarin hydrazide-hydrazone derivatives (CHHD), whereas BCHHD's 8c and 10c showed significant antiproliferative activity only against resistant Panc-1 cells with IC50 of 2.02 mu M and 2.15 mu M, respectively. All the investigated BCHHD's were able to activate caspases 3/7 and they could induce apoptosis in resistant Panc-1 cells. Microarray analysis showed that BCHHD 7c induced the expression of apoptotic- and cell cycle arrest (G2/M)- genes in resistant Panc-1 cells. Moreover, BCHHD 7c induced the up-regulation of CDKN1A, DDIT4, GDF-15 and down-regulation of CDC2, CDC20, CDK2 genes. Based on our results, we conclude that 7c could be a potent anticancer drug to overcome drug resistance in cancer and it could be highly beneficial for patients in the clinic. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.02.026

文献信息

• Anticancer activity of new coumarin substituted hydrazide–hydrazone derivatives
  作者：Tamer Nasr、Samir Bondock、Mahmoud Youns

  DOI：10.1016/j.ejmech.2014.02.026

  日期：2014.4

  Drug resistance is a major impediment for cancer treatment, to overcome it we designed and synthesized sixteen coumarins bearing hydrazide-hydrazone moiety and evaluated them against human drug-resistant pancreatic carcinoma (Panc-1) cells and drug-sensitive (hepatic carcinoma; Hep-G2 and leukemia; CCRF) cell lines in vitro. The 6-brominated coumarin hydrazide-hydrazone derivatives (BCHHD) 7c, 8c and 10c were more potent than doxorubicin (DOX) against resistant Panc-1 cells. BCHHD 7c showed significant cytotoxicity against all tested cells (IC50: 3.60-6.50 mu M) on comparison with all other coumarin hydrazide-hydrazone derivatives (CHHD), whereas BCHHD's 8c and 10c showed significant antiproliferative activity only against resistant Panc-1 cells with IC50 of 2.02 mu M and 2.15 mu M, respectively. All the investigated BCHHD's were able to activate caspases 3/7 and they could induce apoptosis in resistant Panc-1 cells. Microarray analysis showed that BCHHD 7c induced the expression of apoptotic- and cell cycle arrest (G2/M)- genes in resistant Panc-1 cells. Moreover, BCHHD 7c induced the up-regulation of CDKN1A, DDIT4, GDF-15 and down-regulation of CDC2, CDC20, CDK2 genes. Based on our results, we conclude that 7c could be a potent anticancer drug to overcome drug resistance in cancer and it could be highly beneficial for patients in the clinic. (C) 2014 Elsevier Masson SAS. All rights reserved.