10-O-((E)-4-(3-oxo-3-(4-phenylpiperazin-1-yl)prop-1-enyl)phenyl)-(10S)-dihydroartemisinin

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 10-O-((E)-4-(3-oxo-3-(4-phenylpiperazin-1-yl)prop-1-enyl)phenyl)-(10S)-dihydroartemisinin
• 英文别名: (10S)-O-{4-[3-oxo-3-(4-phenylpiperazin-1-yl)-1-(E)-propen-1-yl]phenyl}dihydroartemisinin；(E)-1-(4-phenylpiperazin-1-yl)-3-[4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]phenyl]prop-2-en-1-one
• 化学式: C₃₄H₄₂N₂O₆
• 分子量: 574.717
• InChiKey: XOMWBXMGGYXPFI-SSODMBQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  42
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  双氢青蒿素 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.5h， 生成 10-O-((E)-4-(3-oxo-3-(4-phenylpiperazin-1-yl)prop-1-enyl)phenyl)-(10S)-dihydroartemisinin
  参考文献：
  名称：

  Combating P-glycoprotein-mediated multidrug resistance with 10- O -phenyl dihydroartemisinin ethers in MCF-7 cells

  摘要：

  A series of 10-beta-phenyl ethers of dihydroartemisinin (DHA) with piperazine substitutions were synthesized with the goal of overcoming multidrug resistance in cancer therapy. These novel compounds exerted significant antiproliferative activities in breast cancer MCF-7 and MCF-7/Adr cell lines at the submicromolar level and were shown to be approximately 100- to 300-times more potent than the lead compound DHA. Remarkably, the P-gp-overexpressed MCF-7/Adr cell line showed collateral sensitivity towards these derivatives. Furthermore, compounds 3d and 5c, with the highest selectivity for MCF-7/Adr towards MCF-7 cells, were free from P-gp efflux in a MDCK-MDR1 assay. Flow cytometry and western blot assays suggested that the antiproliferative effects of 5c were associated with cell cycle arrest at G1 phase through the downregulation of Cyclin D1 and Cyclin B1. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.10.040

文献信息

• Combating P-glycoprotein-mediated multidrug resistance with 10- O -phenyl dihydroartemisinin ethers in MCF-7 cells
  作者：Hang Zhong、Xuan Zhao、Zhizhong Zuo、Jingwei Sun、Yao Yao、Tao Wang、Dan Liu、Linxiang Zhao

  DOI：10.1016/j.ejmech.2015.10.040

  日期：2016.1

  A series of 10-beta-phenyl ethers of dihydroartemisinin (DHA) with piperazine substitutions were synthesized with the goal of overcoming multidrug resistance in cancer therapy. These novel compounds exerted significant antiproliferative activities in breast cancer MCF-7 and MCF-7/Adr cell lines at the submicromolar level and were shown to be approximately 100- to 300-times more potent than the lead compound DHA. Remarkably, the P-gp-overexpressed MCF-7/Adr cell line showed collateral sensitivity towards these derivatives. Furthermore, compounds 3d and 5c, with the highest selectivity for MCF-7/Adr towards MCF-7 cells, were free from P-gp efflux in a MDCK-MDR1 assay. Flow cytometry and western blot assays suggested that the antiproliferative effects of 5c were associated with cell cycle arrest at G1 phase through the downregulation of Cyclin D1 and Cyclin B1. (C) 2015 Published by Elsevier Masson SAS.