3-hydroxyiminoolean-12-en-28-oic acid morpholide | 55732-16-6

• 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: 3-hydroxyiminoolean-12-en-28-oic acid morpholide
• 英文别名: 4-(3-hydroxyimino-olean-12-en-28-oyl)-morpholine；N-(3-Hydroxyiminoolean-12-en-28-oyl)-morpholine
• CAS: 55732-16-6
• 化学式: C₃₄H₅₄N₂O₃
• 分子量: 538.814
• InChiKey: SHRKAOGSXBPNBI-QWHZRCHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.48
• 重原子数：
  39.0
• 可旋转键数：
  1.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  62.13
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-hydroxyiminoolean-12-en-28-oic acid morpholide 在 对甲苯磺酰氯 作用下， 以 吡啶 为溶剂， 生成 3-oxo-3a-aza-A-homoolean-12-en-28-oic acid morpholide
  参考文献：
  名称：

  Syntheses of Nitrogen-containing Triterpenes. III. Derivatives of Betulinic Acid and Oleanolic Acid

  摘要：

  DOI：

  10.1248/yakushi1947.94.11_1468
• 作为产物：
  描述：

  3-acetyl oleanolic acid chloride 在 Jones reagent 、 盐酸羟胺 、 sodium acetate 、 sodium hydroxide 作用下， 以 乙醇 、 丙酮 、 苯 为溶剂， 反应 1.0h， 生成 3-hydroxyiminoolean-12-en-28-oic acid morpholide
  参考文献：
  名称：

  简单的齐墩果酸酰胺作为有效的渗透促进剂。

  摘要：

  透皮运输现在正成为最便捷，最安全的药物输送途径之一。在某些情况下，有必要使用皮肤渗透促进剂，以实现透皮运输药物，否则这些药物就不能充分渗透皮肤。通过多步合成形成了一系列齐墩果酸酰胺作为潜在的透皮渗透促进剂，并提出了所有新制备的化合物的合成。测试了齐墩果酸的合成酰胺的体外渗透促进剂活性。通过使用Fürst方法评估上述活性。介绍了所研究化合物的化学结构与渗透活性之间的关系。

  DOI：

  10.1371/journal.pone.0122857

文献信息

• Synthesis of new potential anticancer agents based on 4-thiazolidinone and oleanane scaffolds
  作者：Danylo Kaminskyy、Barbara Bednarczyk-Cwynar、Olexandr Vasylenko、Oxana Kazakova、Borys Zimenkovsky、Lucjusz Zaprutko、Roman Lesyk

  DOI：10.1007/s00044-011-9893-9

  日期：2012.11

  The synthesis and evaluation of the anticancer activity of new acylated oximes derivatives of oleanolic acid with 4-thiazolidinone-3(5)-carboxylic acid moieties were described. Newly synthesized compounds were elucidated on the basis of elemental analyses and spectral data (IR, 1H, and 13C NMR). Anticancer activity of the tested compounds has been evaluated in vitro at National Cancer Institute (NCI)

  描述了齐墩果酸的新酰化肟衍生物与4-噻唑烷酮-3（5）-羧酸部分的合成和抗癌活性的评价。根据元素分析和光谱数据（IR，1 H和13 C NMR）阐明了新合成的化合物。已在美国国家癌症研究所（NCI）评估了被测化合物的抗癌活性，其中讨论了一些结构活性关系（SAR）。在测试的化合物中，3-[（2,4-噻唑烷二酮-5-亚甲基）-羧基亚氨基]油酸酯-12-en-28-油酸甲酯（IVm）优于其他相关化合物，pGI的平均值为50  = 5.51 / 5.57，pTGI = 5.09 / 5.13和pLC 50 = 4.62 / 4.64，体内空心纤维测定的低毒性和中等活性水平。
• Oleanolic acid oxime derivatives and their conjugates with aspirin modulate the NF-κB-mediated transcription in HepG2 hepatoma cells
  作者：Violetta Krajka-Kuźniak、Barbara Bednarczyk-Cwynar、Jarosław Paluszczak、Hanna Szaefer、Maria Narożna、Lucjusz Zaprutko、Wanda Baer-Dubowska

  DOI：10.1016/j.bioorg.2019.103326

  日期：2019.12

  The aim of this study was to evaluate the effect of new oleanolic acid oxime (OAO) derivatives and their conjugates with aspirin (ASP) on the expression and activation of NF-kappa B in human hepatoma HepG2 cells. OAO derivatives showed a stronger cytotoxic effect against HepG2 cells compared with their conjugates with aspirin. Moreover, conjugation of OAO with ASP led to enhanced downregulation of NF-kappa B expression and activation. Among the hybrids with ASP, compounds: 19, 3-(2-acetoxy)benzoyloxyiminoolean-12-en-28-oic acid morpholide and 13, 3-(2-acetoxy)benzoyloxyiminoolean-12-en-28-oic acid methyl ester, differing, respectively, in morpholide and methyl ester groups at the C-17 position of oleanolic acid (OA) molecule were the most efficient. COX-2 transcript and protein levels were also diminished after treatment with these compounds. The results of this study indicate that the new derivatives of OAO and particularly their conjugates with ASP, downregulate the expression of COX-2 in HepG2 cells by modulating the NF-kappa B signaling pathway and suggest their potential application in the prevention of liver inflammation and cancer.
• Activation of the Nrf2 response by oleanolic acid oxime morpholide (3-hydroxyiminoolean-12-en-28-oic acid morpholide) is associated with its ability to induce apoptosis and inhibit proliferation in HepG2 hepatoma cells
  作者：Maria Narożna、Violetta Krajka-Kuźniak、Robert Kleszcz、Barbara Bednarczyk-Cwynar、Hanna Szaefer、Wanda Baer-Dubowska

  DOI：10.1016/j.ejphar.2020.173307

  日期：2020.9

  Our previous study demonstrated that new oleanolic acid oxime (OAO) derivatives and their conjugates with aspirin (ASP) inhibit NF-kappa B activation. Evidence exists that the downregulation of NF-kappa B negatively interferes with the Nrf2 signaling pathway. This study aimed to evaluate the effect of these compounds on Nrf2 activation and its cellular consequences in human hepatoma HepG2 cells and immortalized normal hepatocytes THLE-2. The results showed the enhanced activation and expression of Nrf2 as a result of treatment with OAO derivatives themselves and to less extent by their ASP conjugates, mainly in HepG2 cells. The association between cytotoxicity evaluated in our previous study and Nrf2 activation was observed. In this regard, compounds (18) with morpholide substituent at the C-17 position of OAO molecule and (12) with methyl ester substituent at the same position of OAO molecule to the most extent activated Nrf2 and subsequently cell cycle arrest at G2/M, leading to increased apoptosis and the number of resting HepG2 cells. The derivative of OAO (18) substituted with ASP (19) also affected Nrf2 activation and expression, but this effect was less pronounced in comparison with non-conjugated OAO. However, conjugation enhanced Nrf2 activation in normal THLE-2 cells. These results confirmed our earlier suggestion that OAO derivatives conjugated with ASP have the potential for application in the liver cancer chemoprevention. OAO themselves, particularly OAO substituted with morpholide, may be considered therapeutic agents, which may support conventional treatment strategy. Further studies are required to confirm this suggestion.
• Bednarczyk-Cwynar, Barbara; Ruszkowski, Piotr; Atamanyuk, Dmytro, Acta poloniae pharmaceutica, 2017, vol. 74, # 3, p. 827 - 835
  作者：Bednarczyk-Cwynar, Barbara、Ruszkowski, Piotr、Atamanyuk, Dmytro、Lesyk, Roman、Zaprutko, Lucjusz

  DOI：——

  日期：——