(3β)-3-acetyloxy-N-hydroxyolean-12-en-28-amide

• 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)-3-acetyloxy-N-hydroxyolean-12-en-28-amide
• 英文别名: [(3S,4aR,6aR,6bS,8aS,12aS,14aR,14bR)-8a-(hydroxycarbamoyl)-4,4,6a,6b,11,11,14b-heptamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl] acetate
• 化学式: C₃₂H₅₁NO₄
• 分子量: 513.761
• InChiKey: MFXQCOFKAFDYKQ-DFHVBEEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3β)-3-acetyloxy-N-hydroxyolean-12-en-28-amide 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 96.0h， 以98%的产率得到(3β)-3,N-dihydroxyolean-12-en-28-amide
  参考文献：
  名称：

  Targeting cancer cells with oleanolic and ursolic acid derived hydroxamates

  摘要：

  Oleanolic and ursolic acid derived hydroxamates were easily obtained from their parent compounds; they were screened for their cytotoxicity applying SRB assays employing several human tumor cell lines. Low EC50 values were determined for compounds in which the nitrogen as well as the oxygen in the hydroxamic acid part still holds acidic hydrogens. Thus, ursolic acid derived compounds having at least an OH and/or NH moiety in the hydroxamate part of the molecule showed good cytotoxicity but they are significantly less selective for the tumor cells than oleanolic acid derived compounds. Good results were determined for oleanolic acid derived 7 for tumor cell lines 518A2 (melanoma, EC50 = 3.3 mu M), A2780 (ovarian carcinoma, EC50 = 3.4 mu M) and HT29 (colon adenocarcinoma, EC50 = 5.6 mu M) while being significantly less cytotoxic for fibroblasts (EC50 = 20.4 mu M). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.064
• 作为产物：
  描述：

  齐墩果酸 在 吡啶 、 4-二甲氨基吡啶 、 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 29.0h， 生成 (3β)-3-acetyloxy-N-hydroxyolean-12-en-28-amide
  参考文献：
  名称：

  Targeting cancer cells with oleanolic and ursolic acid derived hydroxamates

  摘要：

  Oleanolic and ursolic acid derived hydroxamates were easily obtained from their parent compounds; they were screened for their cytotoxicity applying SRB assays employing several human tumor cell lines. Low EC50 values were determined for compounds in which the nitrogen as well as the oxygen in the hydroxamic acid part still holds acidic hydrogens. Thus, ursolic acid derived compounds having at least an OH and/or NH moiety in the hydroxamate part of the molecule showed good cytotoxicity but they are significantly less selective for the tumor cells than oleanolic acid derived compounds. Good results were determined for oleanolic acid derived 7 for tumor cell lines 518A2 (melanoma, EC50 = 3.3 mu M), A2780 (ovarian carcinoma, EC50 = 3.4 mu M) and HT29 (colon adenocarcinoma, EC50 = 5.6 mu M) while being significantly less cytotoxic for fibroblasts (EC50 = 20.4 mu M). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.064

文献信息

• Targeting cancer cells with oleanolic and ursolic acid derived hydroxamates
  作者：Jana Wiemann、Lucie Heller、René Csuk

  DOI：10.1016/j.bmcl.2015.12.064

  日期：2016.2

  Oleanolic and ursolic acid derived hydroxamates were easily obtained from their parent compounds; they were screened for their cytotoxicity applying SRB assays employing several human tumor cell lines. Low EC50 values were determined for compounds in which the nitrogen as well as the oxygen in the hydroxamic acid part still holds acidic hydrogens. Thus, ursolic acid derived compounds having at least an OH and/or NH moiety in the hydroxamate part of the molecule showed good cytotoxicity but they are significantly less selective for the tumor cells than oleanolic acid derived compounds. Good results were determined for oleanolic acid derived 7 for tumor cell lines 518A2 (melanoma, EC50 = 3.3 mu M), A2780 (ovarian carcinoma, EC50 = 3.4 mu M) and HT29 (colon adenocarcinoma, EC50 = 5.6 mu M) while being significantly less cytotoxic for fibroblasts (EC50 = 20.4 mu M). (C) 2015 Elsevier Ltd. All rights reserved.
• Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors
  作者：Alberto Minassi、Federica Rogati、Cristina Cruz、M. Eugenia Prados、Nuria Galera、Carla Jinénez、Giovanni Appendino、M. Luz Bellido、Marco A Calzado、Diego Caprioglio、Eduardo Muñoz

  DOI：10.1021/acs.jnatprod.8b00514

  日期：2018.10.26

  Pentacyclic triterpenoid acids (PCTTAs) are pleiotropic agents that target many macromolecular endpoints with low to moderate affinity. To explore the biological space associated with PCTTAs, we have investigated the carboxylate-to-hydroxamate transformation, discovering that it de-emphasizes affinity for the transcription factors targeted by the natural compounds (NF-kappa B, STAT3, Nrf2, TGRS) and selectively induces inhibitory activity on HIF prolyl hydrolases (PHDs). Activity was reversible, isoform-selective, dependent on the hydroxamate location, and negligible when this group was replaced by other chelating elements or O-alkylated. The hydroxamate of betulinic acid (Sb) was selected for further studies, and evaluation of its effect on HIF-la expression under normal and hypoxic conditions qualified it as a promising lead structure for the discovery of new candidates in the realm of neuroprotection.