18β-11-oxo-olean-12-en-30-oic acid-(6'-bromohexyl)ester | 1370262-43-3

• 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: 18β-11-oxo-olean-12-en-30-oic acid-(6'-bromohexyl)ester
• 英文别名: 6-bromohexyl(3β)-3-hydroxy-11-oxoolean-12-en-oate；6-bromohexyl (2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-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-carboxylate
• CAS: 1370262-43-3
• 化学式: C₃₆H₅₇BrO₄
• 分子量: 633.75
• InChiKey: IXPQOVLMLPXTNL-KNPCULJYSA-N

物化性质

• 沸点：
  656.8±55.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  18β-11-oxo-olean-12-en-30-oic acid-(6'-bromohexyl)ester 在 Jones reagent 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 1.0h， 生成 18β-3,11-dioxo-olean-12-en-30-oic acid-(6'-triphenylphosphonio-caproate bromide) ester
  参考文献：
  名称：

  Mitochondria-targeted triphenylphosphonium conjugated glycyrrhetinic acid derivatives as potent anticancer drugs

  摘要：

  Glycyrrhetinic acid has been usually studied for their anti-tumor activities. However, the low bioavailability and poor aqueous solubility as well as limited intracellular accumulation have limited their utility. In this present study, a series of new glycyrrhetinic acid conjugates with a triphenylphosphonium cation (TTP+) moiety, meant to specifically target them to tumor cells mitochondria, have been designed and synthesized. Among them, compound 2f possessed excellent antitumor activities against the tested human cancer cells, and simultaneously exhibited better cell selectivity between cancer cells and normal cells than glycyrrhetinic acid and HCPT. Moreover, 2f significantly induced cell cycle arrest at the G2/M phase, and effectively inhibited cancer cells proliferation and migration. Mechanism studies revealed that 2f triggered apoptosis through the mitochondrial pathway via the collapse of mitochondrial membrane potential, reactive oxygen species production and the activation of caspase-9 and caspase-3.

  DOI：

  10.1016/j.bioorg.2018.12.036
• 作为产物：
  描述：

  1,6-二溴己烷 、 甘草次酸 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 18β-11-oxo-olean-12-en-30-oic acid-(6'-bromohexyl)ester
  参考文献：
  名称：

  齐墩果酸/熊果酸/甘草次酸-硫化氢供体杂合物的合成及其抗肿瘤活性

  摘要：

  根据关于硫化氢供体分子和齐墩果酸衍生物抗肿瘤活性的启发性报告，总共设计，合成和评估了25种靶向的硫化氢供体-五环三萜杂化物。结果表明，只有一些杂种（10a，10b，12a，12b，13a和15b）显示出对K562细胞系的中等抗增殖活性。这表明，齐墩果烷型，（R）-硫辛酸和TBZ基团更有利于抗增殖活性。此外，在齐墩果烷型中，C-3 OH比C-28 / 29 COOH对（R）-硫辛酸衍生物。其中，仅化合物13a对K562和K562 / ADR细胞系均显示出中等的抗增殖活性，而对BEL-7402和L-O2细胞系则没有显示出抗增殖活性。因此，在抗肿瘤领域中，它不适合与齐墩果酸，熊果酸和甘草次酸相连的硫化氢供体的杂交。

  DOI：

  10.1007/s00044-019-02366-w

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。
• 甘草次酸-硫化氢供体试剂衍生物及其合成方 法和应用
  申请人：广西师范大学

  公开号：CN106243182B

  公开（公告）日：2018-11-23

  本发明公开了一种甘草次酸‑硫化氢供体试剂衍生物及其合成方法和应用。该衍生物的合成方法为：取甘草次酸、α,ω‑二溴烷烃和碱在非质子极性溶剂中反应，得到化合物1；取化合物1、硫化氢供体试剂和碱在非质子极性溶剂中反应，得到目标物粗品；其中，反应在加热或不加热的条件下进行。合成得到衍生物中的大部分化合物对慢性骨髓性白血病细胞K562具有一定的抑制活性，有望用于相应的抗肿瘤药物及治疗慢性骨髓性白血病的药物的制备。所述合成得到的衍生物具有下述通式(I)所示结构：其中，n为2～8；R为或
• Synthesis and cytotoxicity of pentacyclic triterpenes‐aniline nitrogen mustard derivatives
  作者：Chun‐Mei Liu、Xiao‐Yan Tian、Chun‐Hua Su、Jia‐Yan Huang、Xiang‐Wu Chu、Sheng‐Ping Deng、Ke‐Guang Cheng

  DOI：10.1002/jccs.201900049

  日期：2020.4

  To discover novel nitrogen mustards, the reported mustard pharmacophore was combined with natural pentacyclic triterpenes, which are characterized with pharmacological and structural diversity. Thus, six conjugates were synthesized with 1,2,3‐triazole linking N,N‐bis (2‐chloroethyl)‐1,4‐phenylenediamine and oleanolic acid, ursolic acid, or glycyrrhetinic acid, and their biological activity was evaluated

  为了发现新的氮芥，将报道的芥菜药效团与天然五环三萜结合起来，其特征在于药理和结构的多样性。因此，合成了六个结合有1,2,3-三唑的N，N-双（2-氯乙基）-1,4-苯二胺和齐墩果酸，熊果酸或甘草次酸的缀合物，并评估了它们对肿瘤的生物学活性。 MTT法检测HeLa，BGC‐823，BEL‐7404和NCI‐H460细胞系。结果，这些缀合物对NCI-H460表现出一定的选择性细胞毒性，尽管它们在四种细胞系中的活性均中等或较弱。
• Synthesis and Cytotoxicity Evaluation of Pentacyclic Triterpene–Phenol Nitrogen Mustard Conjugates
  作者：Jia-yan Huang、Lin-dong Yang、Chun-hua Su、Xiang-wu Chu、Jiang-yu Zhang、Sheng-ping Deng、Ke-guang Cheng

  DOI：10.1007/s10600-018-2270-x

  日期：2018.1

  Using a reported pharmacophore, 4-[N,N-bis(2-chloroethyl)-amino]phenol, and pentacyclic triterpenes, pharmacologically and structurally diverse components of natural products, six pentacyclic triterpene-4-[N,N-bis(2-chloroethyl)-amino]phenol conjugates were synthesized by click chemistry. Their cytotoxicities against the BEL-7404 and NCI-H460 tumor cell lines were evaluated by the MTT assay. The in

  使用已报道的药效团、4-[N,N-双(2-氯乙基)-氨基]苯酚和五环三萜，天然产物的药理和结构多样的成分，六五环三萜-4-[N,N-bis(2 -氯乙基)-氨基]苯酚缀合物通过点击化学合成。通过 MTT 测定评估它们对 BEL-7404 和 NCI-H460 肿瘤细胞系的细胞毒性。细胞毒性试验的体外结果表明，在 20 μM 的化合物浓度下，这些偶联物对培养的受试肿瘤细胞显示出低毒性 (< 16%)。
• Antiproliferative activity of ursolic acid/glycyrrhetinic acid-uracil/thymine hybrids
  作者：Li Sun、Xiang-Wu Chu、Chun-mei Liu、Li-Xin Sheng、Zhuan-Xin Chen、Ke-Guang Cheng

  DOI：10.1007/s00044-019-02344-2

  日期：2019.6

  As pharmacophore hybridization has been used frequently in the discovery of new drugs, ursolic acid/glycyrrhetinic acid-uracil/thymine hybrids have been synthesized and evaluated their antiproliferative activity by the MTT assay. The results displayed that, the hybrids of glycyrrhetinic acid (7a-7b to 10a-10b) exhibited slightly better antiproliferative activity than that of ursolic acid hybrids (3a-3b to 6a-6b). Two single glycyrrhetinic acid-thymine hybrids (8a and 10a) possessed good antiproliferative activity against tested A549 cell line (IC50=10.7 and 18.3 mu M, respectively). And three hybrids (3a, 5a, and 10b) exhibited about 80% inhibitory ratio against tested Hela cell line.