[2-[2-[2-[(3β)-cholest-5-en-3-yloxy]ethoxy]ethoxy]ethoxy]acetic acid | 173308-26-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: [2-[2-[2-[(3β)-cholest-5-en-3-yloxy]ethoxy]ethoxy]ethoxy]acetic acid
• CAS: 173308-26-4
• 化学式: C₃₅H₆₀O₆
• 分子量: 576.858
• InChiKey: JKNMROJLWJKFJH-SJTWHRLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.55
• 重原子数：
  41.0
• 可旋转键数：
  17.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  74.22
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [2-[2-[2-[(3β)-cholest-5-en-3-yloxy]ethoxy]ethoxy]ethoxy]acetic acid 在 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 [2-[2-[2-[(3β)-cholest-5-en-3-yloxy]ethoxy]ethoxy]ethoxy]acetic acid [2-(1,3-dithiol-2-ylidene)-1,3-dithiol-4-yl]methyl ester
  参考文献：
  名称：

  脂质体表面四硫富瓦烯的亚稳态氧化状态†

  摘要：

  氧化还原活性脂质体是通过在磷脂囊泡中掺入四硫富瓦烯-胆固醇共轭物1来制备的。通过UV-可见光谱法监测水溶液中脂质体表面上的四硫富瓦烯（TTF）的氧化。结果表明，由于脂质膜中TTF基团的高局部浓度，形成了单氧化阳离子自由基的亚稳态（TTF +）2π二聚体。这些二聚体可通过添加葫芦[8] uril或通过改变脂质组成而降低膜的横向迁移率来进一步稳定。

  DOI：

  10.1039/c4tb01627k
• 作为产物：
  描述：

  在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 8.0h， 生成 [2-[2-[2-[(3β)-cholest-5-en-3-yloxy]ethoxy]ethoxy]ethoxy]acetic acid
  参考文献：
  名称：

  脂质体主动识别葡萄糖转运蛋白 GLUT1 和整合素 αv β3 用于胶质瘤的双重靶向

  摘要：

  由于血脑屏障（BBB）的存在，胶质瘤的治疗是一个巨大的挑战。为了开发一种有效的胶质瘤靶向药物递送系统以大大提高抗癌药物的脑通透性和靶向胶质瘤，设计并合成了一种新型的胶质瘤靶向葡萄糖-RGD（Glu-RGD）衍生物作为配体制备脂质体有效递送紫杉醇 (PTX) 以穿过 BBB 并靶向神经胶质瘤。脂质体被制备并表征为粒径、zeta 电位、包封效率、释放曲线、稳定性、溶血和细胞毒性。此外，与裸 PTX、未包被、单独修饰的脂质体和通过物理混合共修饰的脂质体相比，Glu-RGD 修饰的脂质体在体外和体内评估中显示出优异的靶向能力。与裸 PTX 相比，相对吸收效率和浓缩效率分别提高了 4.41 和 4.72 倍。此外，与体内成像中的其他组相比，Glu-RGD 修饰的脂质体还在肿瘤部位显示出负载 DiD 的脂质体的最大积累。体外和体内的所有结果表明，Glu-RGD-Lip 将是 PTX 治疗整合素 αvβ3

  DOI：

  10.1002/ardp.201800219

文献信息

• Cytomimetic Modeling in Which One Phospholipid Liposome Chemically Attacks Another
  作者：Fredric M. Menger、Vladimir A. Azov

  DOI：10.1021/ja000504x

  日期：2000.7.1
• Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and preliminary evaluation
  作者：Yao Peng、Yi Zhao、Yang Chen、Zhongzhen Yang、Li Zhang、Wenjiao Xiao、Jincheng Yang、Li Guo、Yong Wu

  DOI：10.1016/j.bmc.2018.08.006

  日期：2018.9

  The treatment of glioma has become a great challenge because of the existence of brain barrier (BB). In order to develop an efficient brain targeting drug delivery system to greatly improve the brain permeability of anti-cancer drugs, a novel brain-targeted glucose-vitamin C (Glu-Vc) derivative was designed and synthesized as liposome ligand for preparing liposome to effectively deliver paclitaxel (PTX). The liposome was prepared and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis and cytotoxicity were also characterized. What's more, the cellular uptake of CFPE-labeled Glu-Vc-Lip on GLUT 1 - and SVCT 2 -overexpressed C6 cells was 4.79-, 1.95-, 4.00- and 1.53-fold higher than that of Lip, Glu-Lip, Vc-Lip and Glu + Vc-Lip. Also, the Glu-Vc modified liposomes showed superior targeting ability in vivo evaluation compared with naked paclitaxel, non-coated, singly-modified and co-modified by physical blending liposomes. The relative uptake efficiency was enhanced by 7.53 fold to that of naked paclitaxel, while the concentration efficiency was up to 7.89 times. What's more, the Glu-Vc modified liposomes also displayed the maximum accumulation of DiD-loaded liposomes at tumor sites with the strongest fluorescence in the brain in vivo imaging. Our results suggest that chemical modification of liposomes with warheads of glucose and vitamin C represents a promising and efficient strategy for the development of brain-specific liposomes drug delivery system by utilizing the endogenous transportation mechanism of the warheads.
• Liposomes modified with double-branched biotin: A novel and effective way to promote breast cancer targeting
  作者：Runxin Lu、Lin Zhou、Qiming Yue、Qijun Liu、Xiaojing Cai、Wenjiao Xiao、Li Hai、Li Guo、Yong Wu

  DOI：10.1016/j.bmc.2019.05.039

  日期：2019.7

  Although active targeting liposomes with cancer-specific ligands can bind and internalize into cancer cells, only a few high-efficiency liposomes have been developed so far because traditional single branched ligand modified liposomes generally failed to deliver adequate therapeutic payload. In this paper, we broke the traditional design concept and synthesized the double branched biotin modified cholesterol (Bio(2)-Chol) for the first time. On this basis, different biotin density modified liposomes ((Bio-Chol) Lip, (Bio-Chol)(2)Lip and (Bio(2)-Chol) Lip) were successfully prepared and used as active targeting drug delivery systems for the treatment of breast cancer. The in vitro and in vivo breast cancer-targeting ability of these liposomes were systemically studied using paclitaxel (PTX) as the model drug. And the uptake mechanism of (Bio(2)-Chol) Lip was investigated. The results showed that (Bio(2)-Chol) Lip had the best breast cancer-targeting ability compared with naked paclitaxel, unmodified Lip, (Bio-Chol) Lip and (Bio-Chol)(2)Lip. In particular, the relative uptake efficiency (RE) and concentration efficiency (CE) of (Bio(2)-Chol) Lip were respectively enhanced by 5.61- and 5.06-fold compared to that of naked paclitaxel. Both distribution data and pharmacokinetic parameters suggested that the double branched biotin modified liposome ((Bio(2)-Chol) Lip) is a very promising drug delivery carrier for breast cancer.