鸦胆子内酯 | 25514-28-7

• 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
• 中文名称: 鸦胆子内酯
• 英文名称: bruceolide
• 英文别名: methyl (1R,2S,3S,3aS,3a¹R,4R,6aR,7aR,11aS,11bR)-1,2,4,9-tetrahydroxy-8,11a-dimethyl-5,10-dioxo-1,4,5,6a,7,7a,10,11,11a,11b-decahydro-2H-3,3a¹-(epoxymethano)dibenzo[de,g]chromene-3(3aH)-carboxylate；methyl (1R,2S,3R,6R,8R,13S,14R,15R,16S,17S)-3,10,15,16-tetrahydroxy-9,13-dimethyl-4,11-dioxo-5,18-dioxapentacyclo[12.5.0.01,6.02,17.08,13]nonadec-9-ene-17-carboxylate
• CAS: 25514-28-7
• 化学式: C₂₁H₂₆O₁₀
• 分子量: 438.431
• InChiKey: YLWQKYSDNGHLAO-PWRINDRCSA-N

物化性质

• 沸点：
  702.8±60.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  鸦胆子内酯 在 吡啶 、 四丁基氟化铵 、 氟化氢吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.5h， 生成 methyl (1R,2S,3R,6R,8R,13S,14R,15R,16S,17S)-10-acetyloxy-3,15,16-trihydroxy-9,13-dimethyl-4,11-dioxo-5,18-dioxapentacyclo[12.5.0.01,6.02,17.08,13]nonadec-9-ene-17-carboxylate
  参考文献：
  名称：

  New Semisynthetic Quassinoids with in Vivo Antimalarial Activity

  摘要：

  On the basis of a comparative analysis for stability in mouse serum between 15-O-acetylbruceolide and bruceolide 15-methyl carbonate, several 3,15-dialkyl carbonates of bruceolide were synthesized and their in vitro antimalarial activity was assessed. Methyl, ethyl, and isopropyl carbonates with pronounced in vitro activity were further evaluated for in vivo antimalarial potency. Both the methyl and ethyl carbonates significantly increased the life span of mice as compared with 3,15-di-O-accetylbruceolide and chloroquine.

  DOI：

  10.1021/jm0201971
• 作为产物：
  描述：

  鸦胆子素 A 在 potassium methanolate 作用下， 以 甲醇 为溶剂， 以32 %的产率得到鸦胆子内酯
  参考文献：
  名称：

  Quassinoid 类似物通过可逆的蛋白质生物合成抑制在人结直肠癌中发挥有效的抗肿瘤活性

  摘要：

  人类结直肠癌 (CRC) 中细胞蛋白质合成加速，CRC 患者蛋白质合成调节因子的高表达与不良预后相关。因此，抑制蛋白质合成可能是结直肠癌的有效治疗策略。我们之前证明了苦木素类鸦胆子醇 (BOL) 对结直肠癌具有抗肿瘤活性。在此，在 BOL 给药后，在两种不同的小鼠模型中观察到有效的肿瘤生长抑制 (>80%) 和 STAT3 抑制。观察到身体和脾脏重量的损失，但在纳米颗粒封装后被消除，同时保持强抗肿瘤活性。 STAT3 siRNA 敲低表现出对细胞增殖的适度抑制。令人惊讶的是，使用 PROTAC 降解剂 (SD-36) 抑制 STAT3 对癌细胞增殖几乎没有影响，这表明苦木素可能存在其他作用机制。 BOL 耐药 (BR) 细胞系 HCT116 BR和 HCA7 BR对标准 CRC 治疗药物和已知的 STAT3 抑制剂同样敏感，但对高三尖杉酯碱 (HHT)（一种已知的蛋白质合成抑制剂）具有耐药性。苦木素抑制蛋白质合成的能力取决于

  DOI：

  10.1016/j.bcp.2023.115564

文献信息

• Quassinoids in Brucea javanica are potent stimulators of lipolysis in adipocytes
  作者：Lucy Lahrita、Kenta Moriai、Ryohei Iwata、Kazuki Itoh、Eisuke Kato

  DOI：10.1016/j.fitote.2019.104250

  日期：2019.9

  for obesity. Quassinoids are unique terpenes found in plants of the Simaroubaceae family, which were recently reported to have lipolytic activity and to suppress weight gain. Brucea javanica is a plant employed in traditional medicines in Asia, which is known to contain various quassinoids. Here, we investigated the lipolytic activity of B. javanica extracts, and identified six quassinoids: brucein A

  肥胖与许多代谢紊乱有关。脂肪分解是脂肪细胞中存储的脂质代谢的第一步，因此被认为是肥胖的治疗靶标。拟南芥是在Simaroubaceae家族的植物中发现的独特萜烯，最近报道它们具有脂解活性并抑制体重增加。布鲁斯爪哇菜是在亚洲传统药物中使用的一种植物，已知含有多种类胡萝卜素。在这里，我们调查了爪哇念珠菌提取物的脂解活性，并鉴定了六种类胡萝卜素：布鲁斯汀A，布鲁斯汀B，布鲁斯汀C，3'-羟基布鲁汀A，布鲁萨特醇和布鲁塞汀醇，它们代表了生物活性成分。B. javanica中所含的类quassinoids在纳摩尔浓度下表现出脂解活性，
• Bruceolides
  申请人：Research Corporation

  公开号：US04350638A1

  公开（公告）日：1982-09-21

  There are provided two synthetic routes to the known potent anti-leukemic quassinoid bruceantin from the more readily available bruceoside-A and -B. Certain of the intermediate compounds produced in the synthetic sequence as well as bruceantin itself have been shown to possess anti-malarial properties.

  提供了两种合成路线，从更容易获得的bruceoside-A和-B合成已知的强效抗白血病的苦杏仁酮bruceantin。在合成过程中产生的某些中间化合物以及bruceantin本身已被证明具有抗疟疾的性质。
• New Semisynthetic Quassinoids with in Vivo Antimalarial Activity
  作者：Nobutoshi Murakami、Masanori Sugimoto、Motoyuki Kawanishi、Satoru Tamura、Hye-Sook Kim、Khurshida Begum、Yusuke Wataya、Motomasa Kobayashi

  DOI：10.1021/jm0201971

  日期：2003.2.1

  On the basis of a comparative analysis for stability in mouse serum between 15-O-acetylbruceolide and bruceolide 15-methyl carbonate, several 3,15-dialkyl carbonates of bruceolide were synthesized and their in vitro antimalarial activity was assessed. Methyl, ethyl, and isopropyl carbonates with pronounced in vitro activity were further evaluated for in vivo antimalarial potency. Both the methyl and ethyl carbonates significantly increased the life span of mice as compared with 3,15-di-O-accetylbruceolide and chloroquine.