1-O-octadecyl-2-hydroxy-sn-glycero-3-phospho-(S)-glycerol

• 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-O-octadecyl-2-hydroxy-sn-glycero-3-phospho-(S)-glycerol
• 英文别名: 1-O-octadecyl-2-lyso-sn-glycero-3-phospho-(S)-glycerol；1-Octadecyl-glycero-3-phospho-(1'-sn-glycerol)；[(2S)-2,3-dihydroxypropyl] [(2R)-2-hydroxy-3-octadecoxypropyl] hydrogen phosphate
• 化学式: C₂₄H₅₁O₈P
• 分子量: 498.638
• InChiKey: TURMXXBJFWCGKW-BJKOFHAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  26
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-O-octadecyl-2-hydroxy-sn-glycero-3-phospho-(S)-glycerol 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 以31 mg的产率得到sodium 1-O-octadecyl-2-hydroxy-sn-glycero-3-phospho-(S)-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
• 作为产物：
  描述：

  硬脂醇 在 palladium on activated charcoal 盐酸 、 叔丁基过氧化氢 、 lithium aluminium tetrahydride 、 三氟甲磺酸 、 三氟化硼乙醚 、 氢气 、 胸苷酸 、 三甲胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 、 癸烷 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 14.67h， 生成 1-O-octadecyl-2-hydroxy-sn-glycero-3-phospho-(S)-glycerol
  参考文献：
  名称：

  Synthesis and Biological Activity of Anticancer Ether Lipids That Are Specifically Released by Phospholipase A₂ in Tumor Tissue

  摘要：

  The clinical use of anticancer lipids is severely limited by their ability to cause lysis of red blood cells prohibiting intravenous injection. Novel delivery systems are therefore required in order to develop anticancer ether lipids (AELs) into clinically useful anticancer drugs. In a recent article (J. Med. Chem. 2004, 4 7, 1694) we showed that it is possible to construct liposome systems composed of masked AELs that are activated by secretory phospholipase A(2) in cancerous tissue. We present here the synthesis of six AELs and evaluate the biological activity of these bioactive lipids. The synthesized AEL 1-6 were tested against three different cancer cell lines. It was found that the stereochemistry of the glycerol headgroup in AEL-2 and 3 has a dramatic effect on the cytotoxicity of the lipids. AEL 1-4 were furthermore evaluated for their ability to prevent phosphorylation of the apoptosis regulating kinase Akt, and a correlation was found between their cytotoxic activity and their ability to inhibit Akt phosphorylation.

  DOI：

  10.1021/jm049006f

文献信息

• Synthesis and Biological Activity of Anticancer Ether Lipids That Are Specifically Released by Phospholipase A₂ in Tumor Tissue
  作者：Thomas L. Andresen、Simon S. Jensen、Robert Madsen、Kent Jørgensen

  DOI：10.1021/jm049006f

  日期：2005.11.1

  The clinical use of anticancer lipids is severely limited by their ability to cause lysis of red blood cells prohibiting intravenous injection. Novel delivery systems are therefore required in order to develop anticancer ether lipids (AELs) into clinically useful anticancer drugs. In a recent article (J. Med. Chem. 2004, 4 7, 1694) we showed that it is possible to construct liposome systems composed of masked AELs that are activated by secretory phospholipase A(2) in cancerous tissue. We present here the synthesis of six AELs and evaluate the biological activity of these bioactive lipids. The synthesized AEL 1-6 were tested against three different cancer cell lines. It was found that the stereochemistry of the glycerol headgroup in AEL-2 and 3 has a dramatic effect on the cytotoxicity of the lipids. AEL 1-4 were furthermore evaluated for their ability to prevent phosphorylation of the apoptosis regulating kinase Akt, and a correlation was found between their cytotoxic activity and their ability to inhibit Akt phosphorylation.
• 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.