calotoxin | 20304-49-8

• 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
• 英文名称: calotoxin
• 英文别名: (1S,3R,5S,7R,8S,9R,10S,12R,14R,15S,18R,19R,22S,23R)-8,9,10,22-tetrahydroxy-7,18-dimethyl-19-(5-oxo-2H-furan-3-yl)-4,6,11-trioxahexacyclo[12.11.0.03,12.05,10.015,23.018,22]pentacosane-14-carbaldehyde
• CAS: 20304-49-8
• 化学式: C₂₉H₄₀O₁₀
• 分子量: 548.631
• InChiKey: LYSHVSOMKBORDM-NFYSVIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  39
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  10

ADMET

毒理性

• 非人类毒性摘录

乳草中毒在牛中仍然是一个牧场主面临的问题，尤其是在没有足够的可饮用牧草或者乳草被混合在割下来的饲料中时。神经和胃肠症状包括抑郁和冷漠、虚弱、失去肌肉控制、跌倒、瞳孔散大、呼吸麻痹、肠道停滞和发酵，偶尔还会出现腹泻。有时还会看到强直性痉挛。症状可能在摄入植物后2小时就开始，并可能持续数小时或数天。中毒的动物在死亡前可能经历一段昏迷期，也可能不会。死亡时的病变包括急性卡他性胃肠炎和肺充血，有时还会涉及肾脏。/乳草中毒/

MILKWEED POISONING IN...CATTLE REMAINS A PROBLEM TO RANCHERS, PARTICULARLY WHEN ADEQUATE QUANTITIES OF POTABLE FORAGE ARE UNAVAILABLE OR WHEN MILKWEEDS ARE INCORPORATED IN CUT FEED. ... NERVOUS & GASTROINTESTINAL SYMPTOMS INCLUDE DEPRESSION AND APATHY, WEAKNESS, LOSS OF MUSCLE CONTROL, FALLING, DILATED PUPILS, RESPIRATORY PARALYSIS, INTESTINAL STASIS AND FERMENTATION, AND OCCASIONALLY, DIARRHEA. SOMETIMES TETANIC SEIZURES ARE SEEN. ...SYMPTOMS MAY BEGIN AS EARLY AS 2 HR AFTER INGESTION OF THE PLANT & MAY CONTINUE FOR HR OR DAYS. A POISONED ANIMAL MAY OR MAY NOT EXPERIENCE A PERIOD OF COMA BEFORE DYING. LESIONS AT DEATH INCLUDE ACUTE CATARRHAL GASTROENTERITIS AND CONGESTION OF THE LUNGS & SOMETIMES OF THE KIDNEYS. /MILKWEED POISONING/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

C procera在沙漠羊中的急性毒性研究，通过口服途径给予单次或多次剂量（6.0至0.001毫升/千克）的乳液，导致死亡。动物出现神经系统症状、排尿、心动过速、呼吸困难和精神状态下降。在肝脏、肾脏、心脏、肺、大脑和肠道中观察到严重的病理变化，与血清中的代谢变化相关。肝脏、心脏和肾脏中总脂质浓度增加。

Acute toxicity of C procera was studied in Desert sheep given single or multiple doses (6.0 to 0.001 ml/kg) of the latex by oral route, it caused death. The animals developed nervous signs, urination, tachycardia, dyspnea and loss of condition. Severe pathological changes were seen in the liver, kidneys, heart, lungs, brain & intestines, correlated with metabolic changes in the serum. The concn of total lipids in the liver, heart and kidneys was increased.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

C procera的急性毒性在沙漠羊中进行了研究，通过静脉途径给予单次或多次剂量（6.0至0.001毫升/千克），它导致了两种动物的死亡。动物出现了神经系统症状、排尿、心动过速、呼吸困难和精神状态下降。在肝脏、肾脏、心脏、肺、大脑和肠中观察到了严重的病理变化，与血清中的代谢变化有关。肝脏、心脏和肾脏中总脂质浓度增加。

Acute toxicity of C procera was studied in Desert sheep given single or multiple doses (6.0 to 0.001 ml/kg) of the latex by iv route, it caused death in both species. The animals developed nervous signs, urination, tachycardia, dyspnea and loss of condition. Severe pathological changes were seen in the liver, kidneys, heart, lungs, brain & intestines, correlated with metabolic changes in the serum. The concn of total lipids in the liver, heart and kidneys was increased.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

C procera的急性毒性在沙漠羊中进行了研究，通过腹腔注射单一或多剂量（6.0至0.001毫升/千克）的乳液，导致死亡。动物出现神经系统症状、排尿、心动过速、呼吸困难和精神状态下降。在肝脏、肾脏、心脏、肺、大脑和肠道中观察到严重的病理变化，与血清中的代谢变化相关。肝脏、心脏和肾脏中总脂质浓度增加。

Acute toxicity of C procera was studied in Desert sheep given single or multiple doses (6.0 to 0.001 ml/kg) of the latex by ip route, it caused death. The animals developed nervous signs, urination, tachycardia, dyspnea and loss of condition. Severe pathological changes were seen in the liver, kidneys, heart, lungs, brain & intestines, correlated with metabolic changes in the serum. The concn of total lipids in the liver, heart and kidneys was increased.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  calotoxin 在 甲醇 、 sodium tetrahydroborate 作用下， 反应 2.0h， 以90%的产率得到19-dihydrocalotoxin
  参考文献：
  名称：

  来自 Calotropis gigantea 的非经典 Cardenolides 作为 HIF-1 抑制剂表现出抗癌作用

  摘要：

  六个新的非经典卡烯内酯（1 - 6），和17级公知的（7 - 23）从分离牛角瓜。除5和7外，所有cardenolides 均显示出对缺氧诱导因子-1 (HIF-1) 转录活性的抑制作用，IC 50为8.85 nM–16.69 µM 。新颖的19-dihydrocalotoxin（1）显示出可比较的HIF-1的抑制活性（IC 50的139.57纳米）地高辛（IC 50 145.77纳米），一个充分研究的HIF-1抑制剂，和11，12，14，16和19表现出比地高辛强 1.4-15.4 倍的 HIF-1 抑制。图 1和11显示出对 HIF-1 α蛋白的剂量依赖性抑制，这导致了它们的 HIF-1 抑制作用。与 LO2 和 H9c2 正常细胞系相比，1和11均显示出对各种癌细胞系的选择性细胞毒性，包括 HCT116、HeLa、HepG2、A549、MCF-7、A2780 和 MDA-MB-231。此外，还得出了这些非经典类心内酯作为

  DOI：

  10.1016/j.bioorg.2021.104740

文献信息

• Non-classical cardenolides from Calotropis gigantea exhibit anticancer effect as HIF-1 inhibitors
  作者：Zhiyuan Zheng、Zhongbo Zhou、Qiulong Zhang、Xiaobo Zhou、Ji Yang、Ming-Rong Yang、Guo-Yuan Zhu、Zhi-Hong Jiang、Ting Li、Qianyu Lin、Li-Ping Bai

  DOI：10.1016/j.bioorg.2021.104740

  日期：2021.4

  Six new non-classical cardenolides (1–6), and seventeen known ones (7–23) were isolated from Calotropis gigantea. All cardenolides showed inhibitory effect on hypoxia inducible factor-1 (HIF-1) transcriptional activity with IC50 of 8.85 nM–16.69 µM except 5 and 7. The novel 19-dihydrocalotoxin (1) exhibited a comparable HIF-1 inhibitory activity (IC50 of 139.57 nM) to digoxin (IC50 of 145.77 nM), a

  六个新的非经典卡烯内酯（1 - 6），和17级公知的（7 - 23）从分离牛角瓜。除5和7外，所有cardenolides 均显示出对缺氧诱导因子-1 (HIF-1) 转录活性的抑制作用，IC 50为8.85 nM–16.69 µM 。新颖的19-dihydrocalotoxin（1）显示出可比较的HIF-1的抑制活性（IC 50的139.57纳米）地高辛（IC 50 145.77纳米），一个充分研究的HIF-1抑制剂，和11，12，14，16和19表现出比地高辛强 1.4-15.4 倍的 HIF-1 抑制。图 1和11显示出对 HIF-1 α蛋白的剂量依赖性抑制，这导致了它们的 HIF-1 抑制作用。与 LO2 和 H9c2 正常细胞系相比，1和11均显示出对各种癌细胞系的选择性细胞毒性，包括 HCT116、HeLa、HepG2、A549、MCF-7、A2780 和 MDA-MB-231。此外，还得出了这些非经典类心内酯作为