2α,3β,23-triacetoxyurs-12-en-28-oic acid | 57688-73-0

• 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: 2α,3β,23-triacetoxyurs-12-en-28-oic acid
• 英文别名: 2α,3β,23-triacetoxyurs-12-ene-28-oic acid；2α,3β,23-triacetoxyursane-12-ene-28-carboxylic acid；asiatic acid triacetate；(2α,3β,4α,6β) 2,3,23-tris(acetyloxy)-urs-12-en-28-oic acid；Asiatic acid triacetate；(1S,2R,4aS,6aR,6aS,6bR,8aR,9R,10R,11R,12aR,14bS)-10,11-diacetyloxy-9-(acetyloxymethyl)-1,2,6a,6b,9,12a-hexamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid
• CAS: 57688-73-0
• 化学式: C₃₆H₅₄O₈
• 分子量: 614.82
• InChiKey: WMGQUBGIICLIJJ-QXNXELDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2α,3β,23-triacetoxyurs-12-en-28-oic acid 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 27.0h， 生成 N-(2α,3β,23-triacetoxyurs-12-ene-28-oyl)diethylamine
  参考文献：
  名称：

  Synthesis and antitumor activity evaluation of new asiatic acid derivatives

  摘要：

  Twelve novel asiatic acid (AA) derivatives were designed and synthesized. Their structures were confirmed using NMR, MS, and IR spectra. Their in vitro cytotoxicities on various cancer cell lines (HeLa, HepG2, BGC-823, and SKOV3) were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Most of the derivatives were found to have stronger cell growth inhibitory activity than AA. Among them, compounds 5-8 and 11 with substituted amide group at C-28 exhibited more potent cytotoxicity than AA, Gefitinib, and etoposide (positive control).

  DOI：

  10.1080/10286020.2012.699961
• 作为产物：
  描述：

  积雪草苷 在 吡啶 、 甲醇 、 sodium hydroxide 作用下， 反应 8.0h， 生成 2α,3β,23-triacetoxyurs-12-en-28-oic acid
  参考文献：
  名称：

  含有[小α]-氨基膦酸酯的新型积雪草酸衍生物的合成，抗增殖和诱导细胞凋亡的作用

  摘要：

  这是已接受的手稿，已通过RSC出版同行评审过程，并已被接受出版。接受的手稿在接受后不久就会在线发布。一旦可用，此版本的文章将被完全编辑，格式化并提供高级阅读的高级文章代替。

  DOI：

  10.1039/c6ra11397d

文献信息

• Synthesis of asiatic acid derivatives and their cytotoxic activity
  作者：Loc Tran Van、Quynh Nhu Vo Thi、Chien Tran Van、Phuong Thao Tran Thi、Ninh Pham Thi、Thanh Nguyen Tuan、Thu Ha Le Thi、Nga Nguyen Thi、Thao Do Thi、Sung Tran Van

  DOI：10.1007/s00044-018-2176-y

  日期：2018.6

  mouth), HepG2 (human hepatocellular carcinoma), and SK-LU-1 (human lung carcinoma). Eleven of the tested compounds, including nine newly synthesized and two known ones showed very strong activity against three tested cell lines with the IC50 values ranging from 0.67 to 37.39 µM. Three compounds showed good activity against KB and HepG2 cell lines with the IC50 values ranging from 1.95 to 32.12 µM. The activity

  二十八个化合物，包括24个新的（4 - 22，25 - 26，和28 - 30）和四个已知的（2，23，24，和27）已经合成从积雪草酸（起始1），将其从分离积雪草。制备方法包括乙酰化，在2-，3-，23-和侧链羟基，氨基上的水解以及28-羧基的酰胺化。所有合成的衍生物在结构上均通过1 H，13确认1 H NMR和MS光谱。此外，还评估了它们对三种癌细胞系的细胞毒性：KB（口腔中的人类癌症），HepG2（人类肝细胞癌）和SK-LU-1（人类肺癌）。测试的化合物中有11种，包括9种新合成的化合物和2种已知化合物，对三种测试细胞系表现出非常强的活性，IC 50值为0.67至37.39 µM。三种化合物对带有IC 50的KB和HepG2细胞系均表现出良好的活性值范围从1.95到32.12 µM。针对KB和HepG2细胞系的活性通常高于针对SK-LU-1细胞系的活性。A环上的羟基和酰胺侧链上的OH
• Synthesis and discovery of asiatic acid based 1,2,3-triazole derivatives as antitumor agents blocking NF-κB activation and cell migration
  作者：Ri-Zhen Huang、Gui-Bin Liang、Mei-Shan Li、Yi-Lin Fang、Shi-Feng Zhao、Mei-Mei Zhou、Zhi-Xin Liao、Jing Sun、Heng-Shan Wang

  DOI：10.1039/c8md00620b

  日期：——

  A series of asiatic acid (AA) based 1,2,3-triazole derivatives were designed, synthesized and subjected to a cell-based NF-κB inhibition screening assay. Among the tested compounds, compound 6k displayed impressive NF-κB inhibitory activity with an IC50 value in the low micromolar range. A molecular docking study was performed to reveal key interactions between 6k and NF-κB in which the 1,2,3-triazole

  设计、合成了一系列基于积雪草酸 (AA) 的 1,2,3-三唑衍生物，并对其进行了基于细胞的 NF-κB 抑制筛选试验。在测试的化合物中，化合物 6k 显示出令人印象深刻的 NF-κB 抑制活性，IC50 值在低微摩尔范围内。进行分子对接研究以揭示 6k 和 NF-κB 之间的关键相互作用，其中 1,2,3-三唑部分和 AA 骨架的羟基对提高抑制活性很重要。随后，表面等离子共振分析验证了化合物 6k 与 NF-κB 蛋白之间的高亲和力，平衡解离常数 (KD) 值为 0.36 μM。进一步的研究表明，化合物 6k 显着抑制了 NF-κB DNA 结合、核转位和 IκBα 磷酸化。而且，体外抗肿瘤活性筛选显示，化合物 6k (IC50 = 2.67 ± 0.06 μM) 对 A549 细胞表现出最好的抗癌活性，至少部分是通过抑制 NF-κB 的活性。此外，用化合物 6k 处理 A549 细胞导
• Synthesis, Anti-Tumor and Anti-Angiogenic Activity Evaluations of Asiatic Acid Amino Acid Derivatives
  作者：Yue Jing、Gang Wang、Ying Ge、Minjie Xu、Zhunan Gong

  DOI：10.3390/molecules20047309

  日期：——

  Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 4–10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 11–17 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.

  合成了十五种亚洲酸（AA）的半合成衍生物，并评估了它们的生物活性。通过NMR、MS和IR光谱确认了这些化合物在C-2、C-3、C-23和C-28位的成功修改。此外，它们的抗肿瘤效果通过不同的癌细胞系（HeLa、HepG2、B16F10、SGC7901、A549、MCF7和PC3）进行了体外评估，而抗血管生成活性则通过使用幼体斑马鱼模型进行了体内评估。在这些衍生物中，化合物4-10显示出比AA更强的细胞毒性和抗血管生成效果，而化合物11-17的效果明显较弱。新的衍生物10也被纳入最终配方中，通过HPLC评估其稳定性，以便其潜在的外用效果。衍生物10的抗肿瘤活性明显优于AA和其他衍生物，其稳定性与母体化合物AA相似。
• Synthesis and antitumor activity evaluation of asiatic acid derivatives as survivin inhibitor
  作者：Yan-Qiu Meng、Hua-Bo Cui、Lei Li、Wei-Chen Zhang、Hong-Shuang Pan、Ting-Ting Yu、Wei Li

  DOI：10.1080/10286020.2017.1405940

  日期：2018.9.2

  A series of asiatic acid derivatives were synthesized and their cytotoxicities in vitro against two cancer cell lines (HepG2 and SGC7901) were evaluated by MTT assay. The results showed that compounds I2, I6, and II6 have more potent anticancer activity than that of the positive control drug paclitaxel. The interactions between the compounds I2, I6, and II6 and survivin were also studied by docking

  合成了一系列的积雪草酸衍生物，并通过MTT法评估了它们对两种癌细胞系（HepG2和SGC7901）的体外细胞毒性。结果表明，与阳性对照药物紫杉醇相比，化合物I 2，I 6和II 6具有更强的抗癌活性。还通过对接模拟研究了化合物I 2，I 6和II 6与survivin之间的相互作用。
• Synthesis and Biological Evaluation of Asiatic Acid Derivatives as Inhibitors of Glycogen Phosphorylases
  作者：Liying Zhang、Jun Chen、Yanchun Gong、Jun Liu、Luyong Zhang、Weiyi Hua、Hongbin Sun

  DOI：10.1002/cbdv.200800092

  日期：2009.6

  Twenty-four asiatic acid derivatives have been synthesized and biologically evaluated as inhibitors of glycogen phosphorylase (GP). Within this series of compounds, asiatic acid benzyl ester (23; IC(50)=3.8 microM) exhibited more potent activity than its parent compound 1 (IC(50)=17 microM). SAR Analysis showed that asiatic acid (1) possessing a 2alpha-OH function exhibited more potent GP inhibitory

  已经合成了 24 种积雪草酸衍生物并在生物学上评估了它们作为糖原磷酸化酶 (GP) 的抑制剂。在这一系列的化合物中，积雪草酸苄酯 (23; IC(50)=3.8 microM) 表现出比其母体化合物 1 (IC(50)=17 microM) 更有效的活性。SAR 分析表明，具有 2alpha-OH 功能的积雪草酸 (1) 比具有 2beta-OH 功能的 eriantic acid B (27) 表现出更有效的 GP 抑制活性。需要基于 1 进行进一步的先导优化，以找到更有效的积雪草酸衍生物作为对缺血性糖尿病并发症具有保护作用的抗糖尿病药物。