(2S)-N-[4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl]-2-[di(propan-2-yloxy)phosphorylamino]-3-methylbutanamide | 1099798-43-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (2S)-N-[4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl]-2-[di(propan-2-yloxy)phosphorylamino]-3-methylbutanamide
• CAS: 1099798-43-2
• 化学式: C₂₇H₃₉N₂O₆P
• 分子量: 518.59
• InChiKey: XNAAJBUKRIUGOR-OGJPMFGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  95.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-di-isopropyloxyphosphoryl-Val 、 (E)-4-(3,5-dimethoxystyryl)aniline 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 以71%的产率得到(2S)-N-[4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl]-2-[di(propan-2-yloxy)phosphorylamino]-3-methylbutanamide
  参考文献：
  名称：

  The design, synthesis, and anti-tumor mechanism study of N-phosphoryl amino acid modified resveratrol analogues

  摘要：

  A novel series of trans-N-phosphoryl amino acid modified resveratrol analogues were synthesized and evaluated in vitro for their cytotoxic effects against CNE-1 and CNE-2 cell lines. These analogues showed good anti-proliferative activity, among which 8d, 8e, 8j, and 9d displayed much stronger inhibition effect than resveratrol and 8d showed the most potent activity with IC(50) value at 3.45 +/- 0.82 mu M. The antitumor effects of 8d, 8e, 8j, and 9d were due to the induction of apoptosis, confirmed by the DNA fragmentation and flow cytometry analysis using PI (propidium iodide) staining and Annexin-V-FITC/PI staining assay. The PI staining assay also showed that 8d, 8e, 8j, and 9d caused cell cycles arrest at G(0)-G(1) phase which finally led to cell apoptosis. Further mechanism study on compound 8d against CNE-2 cells has shown the PARP cleavage, which is a hallmark of caspase-3 activation, as well as the activation of caspase-9, and the intracellular ROS generation. These results all suggest that 8d induced a mitochondrial-dependent apoptosis pathway. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.022

文献信息

• The design, synthesis, and anti-tumor mechanism study of N-phosphoryl amino acid modified resveratrol analogues
  作者：Huachen Liu、Aijun Dong、Chunmei Gao、Chunyan Tan、Hongxia Liu、Xuyu Zu、Yuyang Jiang

  DOI：10.1016/j.bmc.2008.10.022

  日期：2008.12

  A novel series of trans-N-phosphoryl amino acid modified resveratrol analogues were synthesized and evaluated in vitro for their cytotoxic effects against CNE-1 and CNE-2 cell lines. These analogues showed good anti-proliferative activity, among which 8d, 8e, 8j, and 9d displayed much stronger inhibition effect than resveratrol and 8d showed the most potent activity with IC(50) value at 3.45 +/- 0.82 mu M. The antitumor effects of 8d, 8e, 8j, and 9d were due to the induction of apoptosis, confirmed by the DNA fragmentation and flow cytometry analysis using PI (propidium iodide) staining and Annexin-V-FITC/PI staining assay. The PI staining assay also showed that 8d, 8e, 8j, and 9d caused cell cycles arrest at G(0)-G(1) phase which finally led to cell apoptosis. Further mechanism study on compound 8d against CNE-2 cells has shown the PARP cleavage, which is a hallmark of caspase-3 activation, as well as the activation of caspase-9, and the intracellular ROS generation. These results all suggest that 8d induced a mitochondrial-dependent apoptosis pathway. (c) 2008 Elsevier Ltd. All rights reserved.