(2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-amino-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 1353569-63-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-amino-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• CAS: 1353569-63-7
• 化学式: C₃₅H₄₃N₃O₁₅
• 分子量: 745.738
• InChiKey: WIUVDUWAESWXAI-SMUIAFOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.66
• 重原子数：
  53.0
• 可旋转键数：
  18.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  234.62
• 氢给体数：
  2.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-amino-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-(((2-((2-hydroxyethyl)disulfaneyl)ethoxy)carbonyl)amino)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  Hepatocyte-Targeting Single Galactose-Appended Naphthalimide: A Tool for Intracellular Thiol Imaging in Vivo

  摘要：

  We present the design, synthesis, spectroscopic properties, and biological evaluation of a single galactose-appended naphthalimide (1). Probe 1 is a multifunctional molecule that incorporates a thiol-specific cleavable disulfide bond, a masked phthalamide fluorophore, and a single galactose moiety as a hepatocyte-targeting unit. It constitutes a new type of targetable ligand for hepatic thiol imaging in living cells and animals. Confocal microscopic imaging experiments reveal that 1, but not the galactose-free control system 2, is preferentially taken up by HepG2 cells through galactose-targeted, ASGP-R-mediated endocytosis. Probe 1 displays a fluorescence emission feature at 540 nm that is induced by exposure to free endogenous thiols, most notably GSH. The liver-specificity of 1 was confirmed in vivo via use of a rat model. The potential utility of this probe in indicating pathogenic states and as a possible screening tool for agents that can manipulate oxidative stress was demonstrated in experiments wherein palmitate was used to induce lipotoxicity in HepG2 cells.

  DOI：

  10.1021/ja210065g
• 作为产物：
  描述：

  3-(6-nitro-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanoic acid 在 4-二甲氨基吡啶 、 palladium on activated charcoal 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(2-(3-(6-amino-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propanamido)ethoxy)ethoxy)ethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  Hepatocyte-Targeting Single Galactose-Appended Naphthalimide: A Tool for Intracellular Thiol Imaging in Vivo

  摘要：

  We present the design, synthesis, spectroscopic properties, and biological evaluation of a single galactose-appended naphthalimide (1). Probe 1 is a multifunctional molecule that incorporates a thiol-specific cleavable disulfide bond, a masked phthalamide fluorophore, and a single galactose moiety as a hepatocyte-targeting unit. It constitutes a new type of targetable ligand for hepatic thiol imaging in living cells and animals. Confocal microscopic imaging experiments reveal that 1, but not the galactose-free control system 2, is preferentially taken up by HepG2 cells through galactose-targeted, ASGP-R-mediated endocytosis. Probe 1 displays a fluorescence emission feature at 540 nm that is induced by exposure to free endogenous thiols, most notably GSH. The liver-specificity of 1 was confirmed in vivo via use of a rat model. The potential utility of this probe in indicating pathogenic states and as a possible screening tool for agents that can manipulate oxidative stress was demonstrated in experiments wherein palmitate was used to induce lipotoxicity in HepG2 cells.

  DOI：

  10.1021/ja210065g

文献信息

• Camptothecin delivery into hepatoma cell line by galactose-appended fluorescent drug delivery system
  作者：Sun Dongbang、Hyun Mi Jeon、Min Hee Lee、Weon Sup Shin、Joon Kook Kwon、Chulhun Kang、Jong Seung Kim

  DOI：10.1039/c4ra02588a

  日期：——

  A galactose-appended camptothecin prodrug was newly synthesized. The prodrug preferentially entered a hepatoma cell line due to the galactose unit and the drug release triggered by disulfide-bond cleavage via reaction with glutathione was visualized on the basis of fluorescence changes of the naphthalimide moiety. The prodrug entered the cells via receptor-mediated endocytosis and released drug molecules into lysosomes, however, the released drug molecules failed to show significant anticancer activity, probably due to lysosomal hydrolysis of their lactone ring converting them to an inactive carboxylate form.

  新合成了一种附着半乳糖的喜树碱前药。由于半乳糖单元的作用，该前药优先进入一种肝癌细胞系，并且通过与谷胱甘肽发生二硫键断裂反应触发药物释放，这一过程可以通过萘酰亚胺部分的荧光变化来可视化观察。该前药通过受体介导的内吞作用进入细胞并在溶酶体中释放药物分子，然而，释放出的药物分子并未表现出显著的抗癌活性，这可能是因为其内酯环在溶酶体中被水解，转化为无活性的羧酸盐形式。