1-octadecanoyl-2-(6-hydroxyhexanoyl)-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol | 1227082-08-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 英文名称: 1-octadecanoyl-2-(6-hydroxyhexanoyl)-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol
• 英文别名: [(2R)-3-[[(2S)-2,3-bis[[tert-butyl(dimethyl)silyl]oxy]propoxy]-(2-cyanoethoxy)phosphoryl]oxy-2-(6-hydroxyhexanoyloxy)propyl] octadecanoate
• CAS: 1227082-08-7
• 化学式: C₄₅H₉₀NO₁₁PSi₂
• 分子量: 908.354
• InChiKey: JEAVHDKKMMOTIQ-DLXBGPHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.74
• 重原子数：
  60
• 可旋转键数：
  42
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  160
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  1-octadecanoyl-2-(6-hydroxyhexanoyl)-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol 、 4-辛基-4-联苯基羧酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release

  摘要：

  The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A(2), the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme.

  DOI：

  10.1021/jm100190c
• 作为产物：
  描述：

  1-octadecanoyl-2-O-(6-(4-methoxybenzyloxy)hexanoyl)-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol 在 水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以82%的产率得到1-octadecanoyl-2-(6-hydroxyhexanoyl)-sn-glycero-3-(2-cyanoethylphospho)-(S)-2,3-O-di-tert-butyldimethylsilyl-glycerol
  参考文献：
  名称：

  Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release

  摘要：

  The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A(2), the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme.

  DOI：

  10.1021/jm100190c

文献信息

• Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release
  作者：Palle J. Pedersen、Sidsel K. Adolph、Arun K. Subramanian、Ahmad Arouri、Thomas L. Andresen、Ole G. Mouritsen、Robert Madsen、Mogens W. Madsen、Günther H. Peters、Mads H. Clausen

  DOI：10.1021/jm100190c

  日期：2010.5.13

  The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A(2), the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme.