葫芦素 IIA | 58546-34-2

• 物质功能分类: 生物化工 - 提取物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 葫芦素 IIA
• 中文别名: 葫芦素IIA；雪胆素甲
• 英文名称: cucurbitacin IIa
• 英文别名: hemslecin A；25-O-acetyl-23,24-dihydrocucurbitacin F；23,24-dihydrocucurbitacin F 25-O-acetate；[(6R)-6-hydroxy-2-methyl-5-oxo-6-[(2S,3S,8S,9R,10R,13R,14S,16R,17R)-2,3,16-trihydroxy-4,4,9,13,14-pentamethyl-11-oxo-1,2,3,7,8,10,12,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]heptan-2-yl] acetate
• CAS: 58546-34-2
• 化学式: C₃₂H₅₀O₈
• 分子量: 562.744
• InChiKey: LKYNAQSYQLFTCM-GYXNDICUSA-N

物化性质

• 沸点：
  679.1±55.0 °C(Predicted)
• 密度：
  1.22
• 溶解度：
  溶于甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• WGK Germany：
  3

制备方法与用途

生物活性

Cucurbitacin IIa 是从园果雪胆中分离得到的一种三萜烯，能够诱导癌细胞凋亡。研究表明，它可降低癌细胞中生存素（survivin）的表达水平，减少磷酸化组蛋白 H3 的水平，并增加裂解的聚腺苷二磷酸核糖聚合酶 (PARP) 的水平。

化学性质

Cucurbitacin IIa 是一种白色结晶粉末，可溶于甲醇、乙醇和 DMSO 等有机溶剂。它来源于葫芦科雪胆属植物。

用途

雪胆素甲具有抑制痢疾杆菌、伤寒杆菌及猪霍乱沙门氏菌的作用。

反应信息

• 作为反应物：
  描述：

  葫芦素 IIA 在 吡啶 、 4-二甲氨基吡啶 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 2,3,16-tri-O-propionyl-5β,6β-epoxy-hemslecin A
  参考文献：
  名称：

  Synthesis of hemslecin A derivatives: A new class of hepatitis B virus inhibitors

  摘要：

  A series of hemslecin A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities, namely, inhibiting the secretion of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA replication on HepG 2.2.15 cells. Most of the derivatives showed enhanced anti-HBV activities, of which compounds A1-A7, B5, C and E exhibited significant activities inhibiting HBV DNA replication with IC50 values of 2.8-11.6 mu M, comparable to that of the positive control, tenofovir. Compounds A1-A3, A5, B5, and C displayed low cytotoxicities, which resulted in high SI values of 89.7, 55.6, 77.8, >83.4, >55.8, and >150.5, respectively. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.024
• 作为产物：
  描述：

  25-O-acetyl-3-O-β-D-glucopyranosyl-23,24-dihydrocucurbitacin F 在 盐酸 作用下， 反应 2.0h， 生成 葫芦素 IIA
  参考文献：
  名称：

  Antidiabetic properties of selected Mexican copalchis of the Rubiaceae family

  摘要：

  The extracts prepared from the stem barks of several Mexican copalchis species, including Hintonia latiflora, Exostema caribaeum and a commercial mixture of Hintonia standleyana and E caribaeum (CM) showed significant hypoglycemic and antihyperglycemic effects. The extracts were tested in three different in vivo models using normal and streptozotocin (STZ)-induced diabetic rats. From the active extract of H. latiflora, 25-O-acetyl-3-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F (1), an analog of 23,24-dihydrocucurbitacin F, and several known compounds (2 8) were isolated; cucurbitacin I was also isolated from H. standleyana. Oral administration of H. latiflora extract [100 mg/kg of body weight (bw)] and 5-O-beta-D-glucopyranosyl-7,3',4'-trihydroxy-4-phenylcoumarin (5) (30 mg/kg of bw) to STZ-induced diabetic rats, for a 30 day duration, restored blood glucose levels to normal values. The groups treated either with the active principle 5, or the extract of H. latiflora, showed less body weight loss than glibenclamide-treated and diabetic control groups (P < 0.05). It was also demonstrated that the extract of H. latiflora regulated hepatic glycogen and plasma insulin levels (p < 0.05). These data suggest that its antihyperglycemic effect is due in part to stimulation of insulin secretion and regulation of hepatic glycogen metabolism. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.phytochem.2007.05.006

文献信息

• 雪胆甲素衍生物及其制备方法和应用
  申请人：山东省医学科学院药物研究所(山东省抗衰老 研究中心、山东省新技术制药研究所)

  公开号：CN110818759B

  公开（公告）日：2021-03-09

  本发明公开了雪胆甲素衍生物其制备方法及其医药用途。具体公开了一类雪胆甲素衍生物(I)，通过雪胆甲素的2，3和16位羟基及其17位支链进行结构修饰，SRB法筛选结果表明：雪胆甲素2，3，16位羟基被乙酰基保护，17位支链被2‑肼基吡啶、2，4，6三氯苯肼或2，4‑二硝基苯肼取代并且羟基被乙酰基保护后的化合物具有较强的抑制肿瘤细胞(SKOV3，LOVO，HT‑29，HepG2，MCF‑7)增殖的作用。同时，这些衍生物对正常细胞HEK293的IC50增大，提示该类衍生物相对于雪胆甲素，其选择性增强。
• Synthesis of cucurbitacin IIa derivatives with apoptosis-inducing capabilities in human cancer cells
  作者：Kun Yu、Xinmei Yang、Ying Li、Xue Cui、Bo Liu、Qingqiang Yao

  DOI：10.1039/c9ra09113k

  日期：——

  cucurbitacin IIa derivatives were synthesized and screened for cytotoxic activity. Their structures were established using 1H NMR, 13C NMR, and LC-MS spectroscopic data. The absolute configuration of the derivatives was determined by single crystal diffraction. In sulforhodamine B (SRB) assays, nearly all compounds displayed low cytotoxicity toward normal human cells (HEK293). However, some derivatives displayed

  合成了 21 种葫芦素 IIa 衍生物并筛选了细胞毒活性。使用1 H NMR、13 C NMR 和 LC-MS 光谱数据确定了它们的结构。衍生物的绝对构型由单晶衍射确定。在磺基罗丹明 B (SRB) 测定中，几乎所有化合物都对正常人体细胞 (HEK293) 表现出低细胞毒性。然而，一些衍生物在低 μM 范围内对几种人类肿瘤细胞系（SKOV3、HT29、HEPG2、MCF-7 和 LOVO）表现出高细胞毒性。获得了低 IC 50值，特别是对于乙酰基保护的产物2、2,4,6-三氯苯肼衍生物4a和 2-肼基吡啶衍生物4d. 特别是，化合物2和4d对 SKOV3 细胞显示出 1.2 ± 0.01 和 2.2 ± 0.19 μM 的低 IC 50值。对这些化合物进行了广泛的生物学测试，结果表明化合物2和4a不会通过影响细胞周期来抑制肿瘤细胞。此外，化合物4a触发了癌细胞中的凋亡途径，显示出高凋亡率。
• Structural revision and pharmacological activity of hemslecin C
  作者：Kun Yu、Xinmei Yang、Ying Li、Xue Cui、Bo Liu、Qingqiang Yao

  DOI：10.1177/1747519819899069

  日期：2020.5

  different from that reported in the literature. The acetyl group of hemslecin A is transferred to the carbonyl α carbon of the side chain and is attacked by the 22-hydroxyl group to give a hemi-acetal that is dehydrated to give hemslecin C. The anticancer activity of this new skeleton is determined by sulforhodamine B assay method, and demonstrates excellent activity, thus providing a new framework

  Hemslecin C 是一种具有新型骨架的化合物，是通过在酒精中用 KOH 回流 hemslecin A 合成的。Hemslecin C 的结构特征是通过比旋光度测量、高分辨率质谱和核磁共振光谱分析。此外，通过X射线单晶测定明确确定了hemslecin C的分子结构。我们发现它的结构与文献报道的不同。hemslecin A 的乙酰基转移到侧链的羰基 α 碳上，并受到 22-羟基的攻击，得到半缩醛，脱水后得到 hemslecin C。这种新骨架的抗癌活性由下式决定磺罗丹明 B 测定方法，并显示出优异的活性，
• Structure revision of cucurbitacin Q1
  作者：Hosny Add El-Fattah

  DOI：10.1016/s0031-9422(00)97030-4

  日期：1994.5

  Abstract Structure revision of curcurbitacin Q 1 is discussed on the basis of spectroscopic data. The stereochemistry of ring A is evaluated and the compound is corrected to be cucurbitacin F 25- O -acetate.

  摘要 基于光谱数据讨论了葫芦素Q 1 的结构修正。评估环A的立体化学并将化合物校正为葫芦素F 25-O-乙酸酯。
• Synthesis of hemslecin A derivatives: A new class of hepatitis B virus inhibitors
  作者：Rui-Hua Guo、Chang-An Geng、Xiao-Yan Huang、Yun-Bao Ma、Quan Zhang、Li-Jun Wang、Xue-Mei Zhang、Rong-Ping Zhang、Ji-Jun Chen

  DOI：10.1016/j.bmcl.2013.01.024

  日期：2013.3

  A series of hemslecin A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities, namely, inhibiting the secretion of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA replication on HepG 2.2.15 cells. Most of the derivatives showed enhanced anti-HBV activities, of which compounds A1-A7, B5, C and E exhibited significant activities inhibiting HBV DNA replication with IC50 values of 2.8-11.6 mu M, comparable to that of the positive control, tenofovir. Compounds A1-A3, A5, B5, and C displayed low cytotoxicities, which resulted in high SI values of 89.7, 55.6, 77.8, >83.4, >55.8, and >150.5, respectively. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.