3β-N-(3-aminopropyl)-3-hydroxy-11-oxoolean-12-en-30-amide | 1237522-71-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3β-N-(3-aminopropyl)-3-hydroxy-11-oxoolean-12-en-30-amide
• 英文别名: (2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-N-(3-aminopropyl)-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxamide
• CAS: 1237522-71-2
• 化学式: C₃₃H₅₄N₂O₃
• 分子量: 526.803
• InChiKey: AICJYSXUHPYYBI-IREBYWSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3β-N-(3-aminopropyl)-3-hydroxy-11-oxoolean-12-en-30-amide 、 2-(4-(((diethoxyphosphoryl)(3-methoxyphenyl)methyl)amino)phenyl)acetic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以86%的产率得到(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-N-[3-[[2-[4-[[diethoxyphosphoryl-(3-methoxyphenyl)methyl]amino]phenyl]acetyl]amino]propyl]-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxamide
  参考文献：
  名称：

  Glycyrrhetinic acid derivatives containing aminophosphonate ester species as multidrug resistance reversers that block the NF-κB pathway and cell proliferation

  摘要：

  Novel NF-kappa B inhibitors based on Glycyrrhetinic acid (GA) derivatives containing aminophosphonate ester moieties were rationally designed and synthesized as well as evaluated their antitumor activities using MIT assay. Many target compounds showed potent antitumor activities against the tested human cancer cell lines including cisplatin-resistant cells, and exhibited significant inhibitory activity to the NF-kappa B with IC50 values at micromolar concentrations in A549 cells, respectively. Among them, compound 12e possessed excellent anti-tumor activities against the tested human cancer cell lines and showed low cytotoxicity toward to human normal liver cells. Moreover, 12e caused obvious loss of MMP and significantly induced ROS production, and displayed inhibition of cell migration against A549 cells in vitro. Importantly, 12e arrested the cell cycle at the S phases and ultimately induced cell apoptosis in A549 cells through blockage of NF-kappa B signaling pathway. Our research provided an efficient strategy for targeting NF-kappa B antitumor drug development.

  DOI：

  10.1016/j.bmcl.2018.10.025
• 作为产物：
  描述：

  在 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 5.75h， 生成 3β-N-(3-aminopropyl)-3-hydroxy-11-oxoolean-12-en-30-amide
  参考文献：
  名称：

  Glycyrrhetinic acid derivatives containing aminophosphonate ester species as multidrug resistance reversers that block the NF-κB pathway and cell proliferation

  摘要：

  Novel NF-kappa B inhibitors based on Glycyrrhetinic acid (GA) derivatives containing aminophosphonate ester moieties were rationally designed and synthesized as well as evaluated their antitumor activities using MIT assay. Many target compounds showed potent antitumor activities against the tested human cancer cell lines including cisplatin-resistant cells, and exhibited significant inhibitory activity to the NF-kappa B with IC50 values at micromolar concentrations in A549 cells, respectively. Among them, compound 12e possessed excellent anti-tumor activities against the tested human cancer cell lines and showed low cytotoxicity toward to human normal liver cells. Moreover, 12e caused obvious loss of MMP and significantly induced ROS production, and displayed inhibition of cell migration against A549 cells in vitro. Importantly, 12e arrested the cell cycle at the S phases and ultimately induced cell apoptosis in A549 cells through blockage of NF-kappa B signaling pathway. Our research provided an efficient strategy for targeting NF-kappa B antitumor drug development.

  DOI：

  10.1016/j.bmcl.2018.10.025

文献信息

• Conversions at C-30 of Glycyrrhetinic Acid and Their Impact on Antitumor Activity
  作者：René Csuk、Stefan Schwarz、Bianka Siewert、Ralph Kluge、Dieter Ströhl

  DOI：10.1002/ardp.201100046

  日期：2012.3

  get “simple” derivatives, for example esters, amides and a nitrile. The influence of these changes on the cytotoxic activity is noteworthy and was determined by a colorimetric sulphorhodamine B test using 7 human tumor cell lines and mouse embryonic fibroblasts (NIH3T3) for comparison. A Trypan blue test as well as an acridine orange/ethidium bromide test was used to discover the ability of the compounds

  甘草根的提取物已用于传统和民间医学，以治疗多种疾病。这些提取物的主要成分是甘草酸。它的苷元甘草次酸具有许多生物活性，其中包括对肿瘤细胞的明显细胞毒性。在这项研究中，我们改变了 C-30 位的甘草次酸以获得“简单”的衍生物，例如酯、酰胺和腈。这些变化对细胞毒活性的影响是值得注意的，并且是通过使用 7 种人类肿瘤细胞系和小鼠胚胎成纤维细胞 (NIH3T3) 进行比色的磺胺罗丹明 B 测试来确定的。台盼蓝试验以及吖啶橙/溴化乙锭试验用于发现化合物诱导细胞凋亡的能力。