methyl N-[3β-acetoxyurs-12-en-28-oyl]-2-amino-3-(p-hydroxyphenyl)propionate

• 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: methyl N-[3β-acetoxyurs-12-en-28-oyl]-2-amino-3-(p-hydroxyphenyl)propionate
• 英文别名: methyl 2-[[(1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-acetyloxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carbonyl]amino]-3-(4-hydroxyphenyl)propanoate
• 化学式: C₄₂H₆₁NO₆
• 分子量: 675.949
• InChiKey: PXCDVVPEHRHMDE-DDORGOLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  49
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl N-[3β-acetoxyurs-12-en-28-oyl]-2-amino-3-(p-hydroxyphenyl)propionate 在 sodium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 3.5h， 以78.3%的产率得到N-[3β-hydroxyurs-12-en-28-oyl]-2-amino-3-(p-hydroxyphenyl)propionic acid
  参考文献：
  名称：

  具有细胞毒活性的熊果酸衍生物的合成及其初步作用机理的研究

  摘要：

  合成了在C-3和C-28位置修饰的19种熊果酸衍生物（15种新化合物）。通过MTT分析评估了衍生物对HeLa，BGC-823和SKOV3细胞的细胞毒活性。通过流式细胞术和DNA片段化评估了衍生物在HeLa细胞中的诱导凋亡和影响细胞周期分布。化合物10b和11b通过诱导凋亡和阻止细胞周期进程，特别具有抑制HeLa细胞生长的活性。检查了典型的“ sub-G1峰”和DNA梯形物的形成，并以剂量​​依赖的方式将细胞周期停滞在S期。

  DOI：

  10.1016/j.bmc.2008.11.036
• 作为产物：
  描述：

  熊果酸 在 吡啶 、 4-二甲氨基吡啶 、 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 methyl N-[3β-acetoxyurs-12-en-28-oyl]-2-amino-3-(p-hydroxyphenyl)propionate
  参考文献：
  名称：

  In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives

  摘要：

  Twenty-three ursolic acid (1) derivatives 2-24 (ten novel compounds 8-10, 14-17 and 22-24) modified at the C-3 and the C-28 positions were synthesized, and their structures were confirmed by IR, (1)H NMR, MS, and elemental analysis. The single crystals of compounds 15 and 17 were obtained. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823, SH-SY5Y, HeLa and HELF cells by the MTT assay. The induction of apoptosis and affects on the cell cycle distribution with compound 14 were assessed by fluorescence microscopy, flow cytometry and the activity of caspase-3 in HepG2 cells. Compounds 14-17 had more significant antiproliferative ability against the four cancer cell lines and low cytotoxicity to human embryonic lung fibroblast cells (HELF). Compounds 11, 14-16, 21 and 23 were particularly active against HepG2 cell growth. Compound 14 was selected to investigate cell apoptosis and cell cycle distribution. Flow cytometric analysis and morphologic changes of the cell exhibited that treatment of HepG2 cells with compound 14 led to cell apoptosis accompanied by cell cycle arrest at the S phase in a dose-dependent manner. Furthermore, the activity of the caspase-3 enzyme was increased in the treated cells. In vivo studies using H22 xenografts in Kunming mice were conducted with compound 14 at doses of 50, 100 and 150 mg/kg body weight The results revealed that the medium dosage group (100 mg/kg) showed significant anticancer activity (45.6 +/- 4.3%) compared to the control group. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.03.050

文献信息

• The synthesis of ursolic acid derivatives with cytotoxic activity and the investigation of their preliminary mechanism of action
  作者：Yan-Qiu Meng、Dan Liu、Ling-Li Cai、Hong Chen、Bo Cao、Yi-Zheng Wang

  DOI：10.1016/j.bmc.2008.11.036

  日期：2009.1

  Nineteen ursolic acid derivatives (15 novel compounds) modified at the C-3 and the C-28 positions were synthesized. The cytotoxic activity of the derivatives was evaluated against HeLa, BGC-823 and SKOV3 cells by MTT assay. Inducing apoptosis and affecting cell cycle distribution by the derivatives in HeLa cells were assessed by flow cytometry and DNA fragmentation. Compounds 10b and 11b were particularly

  合成了在C-3和C-28位置修饰的19种熊果酸衍生物（15种新化合物）。通过MTT分析评估了衍生物对HeLa，BGC-823和SKOV3细胞的细胞毒活性。通过流式细胞术和DNA片段化评估了衍生物在HeLa细胞中的诱导凋亡和影响细胞周期分布。化合物10b和11b通过诱导凋亡和阻止细胞周期进程，特别具有抑制HeLa细胞生长的活性。检查了典型的“ sub-G1峰”和DNA梯形物的形成，并以剂量​​依赖的方式将细胞周期停滞在S期。
• In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives
  作者：Jing-Wei Shao、Yong-Chao Dai、Jin-Ping Xue、Ji-Chuang Wang、Feng-Ping Lin、Yang-Hao Guo

  DOI：10.1016/j.ejmech.2011.03.050

  日期：2011.7

  Twenty-three ursolic acid (1) derivatives 2-24 (ten novel compounds 8-10, 14-17 and 22-24) modified at the C-3 and the C-28 positions were synthesized, and their structures were confirmed by IR, (1)H NMR, MS, and elemental analysis. The single crystals of compounds 15 and 17 were obtained. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823, SH-SY5Y, HeLa and HELF cells by the MTT assay. The induction of apoptosis and affects on the cell cycle distribution with compound 14 were assessed by fluorescence microscopy, flow cytometry and the activity of caspase-3 in HepG2 cells. Compounds 14-17 had more significant antiproliferative ability against the four cancer cell lines and low cytotoxicity to human embryonic lung fibroblast cells (HELF). Compounds 11, 14-16, 21 and 23 were particularly active against HepG2 cell growth. Compound 14 was selected to investigate cell apoptosis and cell cycle distribution. Flow cytometric analysis and morphologic changes of the cell exhibited that treatment of HepG2 cells with compound 14 led to cell apoptosis accompanied by cell cycle arrest at the S phase in a dose-dependent manner. Furthermore, the activity of the caspase-3 enzyme was increased in the treated cells. In vivo studies using H22 xenografts in Kunming mice were conducted with compound 14 at doses of 50, 100 and 150 mg/kg body weight The results revealed that the medium dosage group (100 mg/kg) showed significant anticancer activity (45.6 +/- 4.3%) compared to the control group. (C) 2011 Elsevier Masson SAS. All rights reserved.