22β-hydroxyoleanonic acid | 10545-79-6

• 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: 22β-hydroxyoleanonic acid
• 英文别名: 22β-hydroxy-3-oxo-olean-12-en-28-oic acid；(4R,4aS,6aR,6aS,6bR,8aR,12aR,14bS)-4-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-10-oxo-3,4,5,6,6a,7,8,8a,11,12,13,14b-dodecahydro-1H-picene-4a-carboxylic acid
• CAS: 10545-79-6
• 化学式: C₃₀H₄₆O₄
• 分子量: 470.693
• InChiKey: SSGQNTBKIXJPSE-FHXXJBRDSA-N

物化性质

• 熔点：
  234 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  583.4±50.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  34
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  22β-hydroxyoleanonic acid 生成 3β,22β-bis-benzoyloxy-olean-12-en-28-oic acid methyl ester
  参考文献：
  名称：

  Barton et al., Journal of the Chemical Society, 1954, p. 3689,3691

  摘要：

  DOI：
• 作为产物：
  描述：

  2-[(2S)-7-羰基-2,3-二氢-7H-呋喃并[3,2-g]色烯-2-基]丙烷-2-基β-D-吡喃葡萄糖苷 在 potassium hydroxide 作用下， 反应 6.0h， 生成 22β-hydroxyoleanonic acid
  参考文献：
  名称：

  The synthesis of non-steroidal anti-inflammatory drug (NSAID)–lantadene prodrugs as novel lung adenocarcinoma inhibitors via the inhibition of cyclooxygenase-2 (COX-2), cyclin D1 and TNF-α-induced NF-κB activation

  摘要：

  强效核因子-kappa B（NF-κB）抑制剂与环氧合酶（COX）抑制性非甾体抗炎药物（NSAIDs）的酯共轭物为癌症治疗提供了一种新颖的方法。合成了不同的NSAIDs与五环三萜类化合物3β，22β-二羟基-油烯-12-烯-28-酸（4）的酯前药，以实现对NF-κB和COX-2的双重抑制。结果表明，主要化合物14通过抑制核因子-kappa B激酶（IKK）的激活，抑制核因子-kappa B alpha（IκBα）的降解，并同时下调NF-κB介导的COX-2和细胞周期蛋白D1的蛋白表达，抑制了肿瘤坏死因子-alpha诱导的（TNF-α诱导的）NF-κB激活。此外，化合物14以剂量依赖的方式抑制肺腺癌A549细胞的增殖，并且其IC50值比顺铂高50倍。化合物14在酸性pH下稳定，而在人体血浆中则容易水解释放活性前体。从结果可以推断，lantadene-NSAID前药具有抑制NF-κB和COX-2的双重能力，有望成为针对肺癌的有前景的抗癌候选药物。

  DOI：

  10.1039/c4ra00280f

文献信息

• Isolation optimisation, synthesis, molecular docking and <i>in silico</i> ADMET studies of lantadene a and its derivatives
  作者：Sharad Kumar Suthar、Ajay Hooda、Ankesh Sharma、Sumit Bansal、Jitender Monga、Monika Chauhan、Manu Sharma

  DOI：10.1080/14786419.2020.1752204

  日期：2021.11.2

  the highest affinity. Furthermore, in the in silico ADMET studies, the lead IKK inhibitor (10) was found to be Ames non-toxic, non-carcinogen, and a weak inhibitor of hERG. Isolation optimisation, synthesis, molecular docking and in silico ADMET studies of lantadene a and its derivativesAll authorsSharad Kumar Suthar,Ajay Hooda,Ankesh Sharma,Sumit Bansal,Jitender Monga,Monika Chauhan &Manu Sharmahttps://doi

  摘要 建立了一种从马缨丹叶中提取分离五环三萜类马缨丹A的简便、经济的方法。lantadene A 通过抑制 IKK 介导的 NF-κB 蛋白表现出显着的抗炎和抗癌特性。因此，合成了 lantadene A 的衍生物以进一步优化药效团的抗炎和抗癌活性。将合成的化合物与 IKK 的活性位点对接，以找到最有效的 IKK 抑制剂。分子对接研究表明，3 β ,22 β-二异丁基取代的镧系衍生物 ( 10 ) 以最高的亲和力与 IKK 蛋白结合。此外，在计算机ADMET研究发现，IKK先导抑制剂（10）是Ames无毒、非致癌物，是hERG的弱抑制剂。 lantadene a 及其衍生物的分离优化、合成、分子对接和计算机ADMET 研究所有作者Sharad Kumar Suthar、Ajay Hooda、Ankesh Sharma、Sumit Bansal、Jitender Monga、Monika Chauhan和Manu
• Synthesis of lantadene analogs with marked in vitro inhibition of lung adenocarcinoma and TNF-α induced nuclear factor-kappa B (NF-κB) activation
  作者：Monika、Ankesh Sharma、Sharad Kumar Suthar、Vaibhav Aggarwal、Hong Boon Lee、Manu Sharma

  DOI：10.1016/j.bmcl.2014.06.068

  日期：2014.8

  The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.
• Synthesis and in vitro anticancer studies of novel C-2 arylidene congeners of lantadenes
  作者：Navin K. Tailor、Hong L. Boon、Manu Sharma

  DOI：10.1016/j.ejmech.2013.04.009

  日期：2013.6

  The antitumor pentacyclic triterpenoids, Lantadene A (1) and B (2) were isolated from the leaves of weed Lantana camara L. (Verbenaceae) and were structurally transformed to bioactive intermediates 3-6. The Claisen-Schmidt reaction of 22 beta-hydroxy-3-oxoolean-12-en-28-oic acid (5) with requisite aldehydes afforded 2-arylidene-22 beta-hydroxy-3-oxoolean-12-en-28-oic acids (7-16). The compounds were evaluated for their in-vitro anticancer activity by National Cancer Institute (NCI), USA and some of these compounds showed marked cytotoxicity in micromolar range. The mean graph midpoint (MG_MID) value of compound 3 (MG_MID -5.69) was higher than standard drug cisplatin (MG_MID -5.66) while comparable in case of compound 12 (MG_MID -5.52). The NCI's COMPARE molecular mechanistic analysis showed that these compounds were in significant correlations with activity patterns of mechanistic set of compounds (PCC >= 0.60). (C) 2013 Elsevier Masson SAS. All rights reserved.
• Novel lung adenocarcinoma and nuclear factor-kappa B (NF-κB) inhibitors: Synthesis and evaluation of lantadene congeners
  作者：Sharad Kumar Suthar、Hong L. Boon、Manu Sharma

  DOI：10.1016/j.ejmech.2013.12.052

  日期：2014.3

  The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22 beta hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-kappa B and IKK beta inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 mu mol, respectively against TNF-alpha. induced activation of NF-kappa B. The congeners 12 and 13 exhibited inhibition of IKK beta in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 mu mol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Barton et al., Journal of the Chemical Society, 1954, p. 903,906
  作者：Barton et al.

  DOI：——

  日期：——