10-O-[4-(5-phenyl-1H-3-pyrazolyl)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-[4-(5-phenyl-1H-3-pyrazolyl)phenyl]-(10S)-dihydroartemisinin
• 英文别名: 10-O-(4-(5-phenyl-1H-pyrazol-3-yl)phenyl)-(10S)-dihydroartemisinin；3-phenyl-5-[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]-1H-pyrazole
• 化学式: C₃₀H₃₄N₂O₅
• 分子量: 502.61
• InChiKey: UCHMXLKNSBYUBO-AYSCOMBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-羟基查耳酮 在 ammonium cerium (IV) nitrate 、 偶氮二甲酸二异丙酯 、 水 、 一水合肼 、 三乙胺 、 三苯基膦 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 27.5h， 生成 10-O-[4-(5-phenyl-1H-3-pyrazolyl)phenyl]-(10S)-dihydroartemisinin 、 10-O-[4-(5-phenyl-1H-3-pyrazolyl)phenyl]-(10R)-dihydroartemisinin
  参考文献：
  名称：

  Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin

  摘要：

  Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycinresistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI(50) = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as therapeutic agents to treat drug-resistant cancer. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.10.023

文献信息

• Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin
  作者：Shenglin Luan、Hang Zhong、Xuan Zhao、Jinyu Yang、Yongkui Jing、Dan Liu、Linxiang Zhao

  DOI：10.1016/j.ejmech.2017.10.023

  日期：2017.12

  Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycinresistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI(50) = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as therapeutic agents to treat drug-resistant cancer. (C) 2017 Published by Elsevier Masson SAS.