didodecyl-[2-[[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carbonyl]amino]ethyl]-methylazanium;chloride | 1621175-06-1

• 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: didodecyl-[2-[[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carbonyl]amino]ethyl]-methylazanium;chloride
• CAS: 1621175-06-1
• 化学式: C₄₈H₈₄FN₂O₄*Cl
• 分子量: 807.657
• InChiKey: YIXZSPOWXFWCKO-SLDBTDFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.74
• 重原子数：
  56
• 可旋转键数：
  26
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  地塞米松 在 sodium periodate 、 硫酸 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 48.75h， 生成 didodecyl-[2-[[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carbonyl]amino]ethyl]-methylazanium;chloride
  参考文献：
  名称：

  Cationic lipid-conjugated dexamethasone as a selective antitumor agent

  摘要：

  Dexamethasone (Dex) is one of the highly potent synthetic glucocorticoids. It exhibits prominent anti-inflammatory but moderate anti-proliferative activities. It is widely used along side chemotherapy to alleviate toxic side effects. Additionally, Dex is also a potent inducer of gluconeogenesis. However, its overuse critically desensitizes cells against chemotherapy. Herein, we report on the development of a new class of cationic lipid-Dex conjugates in which the C-8 carbon chain analogue (DX8) exhibited glucocorticoid receptor (GR)-mediated, caspase-3-assisted, cancer cell-selective anti-proliferative activity. Melanoma tumors in DX8-treated mice exhibited significantly reduced tumor aggressiveness with respect to tumors in Dex-treated mice. Tumor lysates prepared from DX8-treated group showed elevated levels of p53. DX8-treated cancer cells showed clear degradation of kinase JAK3/STAT3 protein levels. Additionally, DX8-treatment decreased the level of VEGFR2 in tumor-endothelial cells implying DX8's anti-proliferative roles in both tumor cells and tumor neovascular cells. Collectively, our results demonstrate potent anti-angiogenic, and selective JAK3/STAT3 down-regulating anticancer characteristics of DX8, a new dexamethasone-based antitumor molecule.

  DOI：

  10.1016/j.ejmech.2014.06.051

文献信息

• Cationic lipid-conjugated dexamethasone as a selective antitumor agent
  作者：Samaresh Sau、Rajkumar Banerjee

  DOI：10.1016/j.ejmech.2014.06.051

  日期：2014.8

  Dexamethasone (Dex) is one of the highly potent synthetic glucocorticoids. It exhibits prominent anti-inflammatory but moderate anti-proliferative activities. It is widely used along side chemotherapy to alleviate toxic side effects. Additionally, Dex is also a potent inducer of gluconeogenesis. However, its overuse critically desensitizes cells against chemotherapy. Herein, we report on the development of a new class of cationic lipid-Dex conjugates in which the C-8 carbon chain analogue (DX8) exhibited glucocorticoid receptor (GR)-mediated, caspase-3-assisted, cancer cell-selective anti-proliferative activity. Melanoma tumors in DX8-treated mice exhibited significantly reduced tumor aggressiveness with respect to tumors in Dex-treated mice. Tumor lysates prepared from DX8-treated group showed elevated levels of p53. DX8-treated cancer cells showed clear degradation of kinase JAK3/STAT3 protein levels. Additionally, DX8-treatment decreased the level of VEGFR2 in tumor-endothelial cells implying DX8's anti-proliferative roles in both tumor cells and tumor neovascular cells. Collectively, our results demonstrate potent anti-angiogenic, and selective JAK3/STAT3 down-regulating anticancer characteristics of DX8, a new dexamethasone-based antitumor molecule.