8-O-azelaoyl-14-benzoylaconine

• 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: 8-O-azelaoyl-14-benzoylaconine
• 英文别名: 8-O-(14-benzoylaconine) azelate；9-[[(1S,2R,3R,4R,5R,6S,7S,8R,9R,10R,13R,14R,16S,17S,18R)-4-benzoyloxy-11-ethyl-5,7,14-trihydroxy-6,16,18-trimethoxy-13-(methoxymethyl)-11-azahexacyclo[7.7.2.12,5.01,10.03,8.013,17]nonadecan-8-yl]oxy]-9-oxononanoic acid
• 化学式: C₄₁H₅₉NO₁₃
• 分子量: 773.918
• InChiKey: NMQIGGWFCPOIKC-LDMJWENQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  55
• 可旋转键数：
  19
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  191
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  壬二酸 、 aconitine 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以44%的产率得到8-O-azelaoyl-14-benzoylaconine
  参考文献：
  名称：

  Hemisynthesis and antiproliferative properties of mono-[O-(14-benzoylaconine-8-yl)]esters and bis-[O-(14-benzoylaconine-8-yl)]esters

  摘要：

  A series of mono- and bifunctional acyl compounds, build from the 8-O-azeloyl-14-benzoylaconine scaffold and differing by the length of the alkyl linker chain, were synthesised and evaluated against a panel of human tumour cell lines, A-549 (lung cancer), MCF-7 (breast cancer) and HCT-15 (colon cancer). None of the mono-[O-(14-benzoylaconine-8-yl)]esters displayed in vitro activity against tumour cells (IC50 > 60 mu M). However, three bis-[O-(14-benzoylaconine-8-yl)]esters presented a noticeable in vitro cytotoxic activity, those bearing 7, 8 and 9 carbon atoms between the two aconitine moieties, with IC(50)s ranging between 4 and 28 mu M. The most active, bis[O-(14-benzoylaconine-8-yl)]suberate, was then evaluated in vivo in immunodeficient mice bearing human tumour xenografts originating from MCF-7 and HCT-15 cells. For MCF-7 cells, administration of five doses every 4 days, and weekly administration of 4 doses resulted in T/C percent values of 36% (p = 0.001) and 56% (p = 0.02) on day 45, respectively. For HCT-15 cells, administration of five doses every 3 days resulted in 49% tumour regression on the 25th day (p = 0.00001). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.05.015

文献信息

• Hemisynthesis and antiproliferative properties of mono-[O-(14-benzoylaconine-8-yl)]esters and bis-[O-(14-benzoylaconine-8-yl)]esters
  作者：Ainura Chodoeva、Jean-Jacques Bosc、Jean Guillon、Pierre Costet、Alain Decendit、Jean-Michel Mérillon、Jean-Michel Léger、Christian Jarry、Jacques Robert

  DOI：10.1016/j.ejmech.2012.05.015

  日期：2012.8

  A series of mono- and bifunctional acyl compounds, build from the 8-O-azeloyl-14-benzoylaconine scaffold and differing by the length of the alkyl linker chain, were synthesised and evaluated against a panel of human tumour cell lines, A-549 (lung cancer), MCF-7 (breast cancer) and HCT-15 (colon cancer). None of the mono-[O-(14-benzoylaconine-8-yl)]esters displayed in vitro activity against tumour cells (IC50 > 60 mu M). However, three bis-[O-(14-benzoylaconine-8-yl)]esters presented a noticeable in vitro cytotoxic activity, those bearing 7, 8 and 9 carbon atoms between the two aconitine moieties, with IC(50)s ranging between 4 and 28 mu M. The most active, bis[O-(14-benzoylaconine-8-yl)]suberate, was then evaluated in vivo in immunodeficient mice bearing human tumour xenografts originating from MCF-7 and HCT-15 cells. For MCF-7 cells, administration of five doses every 4 days, and weekly administration of 4 doses resulted in T/C percent values of 36% (p = 0.001) and 56% (p = 0.02) on day 45, respectively. For HCT-15 cells, administration of five doses every 3 days resulted in 49% tumour regression on the 25th day (p = 0.00001). (C) 2012 Elsevier Masson SAS. All rights reserved.