牛角瓜甙 | 1986-70-5

• 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: 牛角瓜甙
• 英文名称: calotropin
• 英文别名: (1S,3R,5S,7R,9S,10S,12R,14R,15S,18R,19R,22S,23R)-9,10,22-trihydroxy-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: 1986-70-5
• 化学式: C₂₉H₄₀O₉
• 分子量: 532.631
• InChiKey: OWPWFVVPBYFKBG-NYVHBPEFSA-N

物化性质

• 熔点：
  223° (dec)
• 比旋光度：
  D18 +66.8° (in methanol)
• 颜色/状态：
  RECTANGULAR PLATELETS FROM ALCOHOL OR ETHYL ACETATE
• 溶解度：
  SOL IN WATER, ALCOHOL; PRACTICALLY INSOL IN ETHER
• 旋光度：
  SPECIFIC OPTICAL ROTATION: +66.8 DEG @ 18 °C/D (IN METHANOL); MAX ABSORPTION: 217 NM (LOG E= 4.21); 310 NM (LOG E= 1.49)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  38
• 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：
  132
• 氢给体数：
  3
• 氢受体数：
  9

ADMET

代谢

早期关于从乳草中分离强心苷的研究是在非洲北部的 Poekilocerus bufonius 草蜢上进行的。这种具有警告色的物种在自然环境中可能专门以乳草为食，它有一个毒腺，其中的内容物可以在若虫阶段作为喷雾喷出，或者在成虫阶段作为泡沫状物质喷出。分泌物中含有组胺和一剂对猫致命的强心苷。当用 Calotropis procera 或 Asclepias curassavica 饲养时，草蜢的分泌物中只含有可观的量级的 Calactin 和 Calotropin，这两种物质是植物中存在的七种或更多相关强心苷中的一部分。

EARLY STUDIES ON CARDENOLIDE SEQUESTRATION FROM MILKWEEDS WERE CARRIED OUT WITH THE GRASSHOPPER, POEKILOCERUS BUFONIUS. THIS APOSEMATIC NORTH AFRICAN SPECIES, WHICH PROBABLY FEEDS EXCLUSIVELY UPON MILKWEEDS IN NATURE, HAS A POISON GLAND FROM WHICH THE CONTENTS MAY BE EJECTED AS SPRAY DURING THE IMMATURE HOPPER STAGE, OR AS A FOAMY FROTH IN THE ADULT STAGE. THE SECRETION CONTAINS HISTAMINE AND ONE CAT-LETHAL DOSE OF CARDENOLIDE. WHEN REARED ON CALOTROPIS PROCERA OR ASCLEPIAS CURASSAVICA, THE GRASSHOPPERS SECRETION CONTAINED ONLY CALACTIN AND CALOTROPIN IN APPRECIABLE QUANTITIES OF THE SEVEN OR SO RELATED CARDENOLIDES PRESENT IN THE PLANT.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在食物植物中，从几种卡丹醇中选择性地储存一些卡丹醇在帝王蝶幼虫中被证实。通过向帝王蝶幼虫分别施用不同剂量的单一卡丹醇，随后分析幼虫和成虫中的卡丹醇含量，证明了代谢转化可能与这种选择性有关。卡拉克汀和卡洛托品被完整储存，但乌沙里丁被代谢为卡拉克汀和卡洛托品的混合物，这些是储存的卡丹醇。这种转化，一种还原作用，在进食过程中非常迅速地发生，显然是在肠道中。提供的解释包括卡拉克汀和卡洛托品可储存而乌沙里丁不可储存的原因，包括后者在肠道环境中的化学不稳定性、极性（卡拉克汀和卡洛托品比乌沙里丁更具极性），以及卡拉克汀和卡洛托品中的C-3'OH可能需要与载体和/或组织储存位点结合的可能性。

SELECTIVE STORAGE OF SOME CARDENOLIDES FROM AMONG SEVERAL IN THE FOOD PLANT WAS CONFIRMED /IN MONARCH LARVAE/... THAT METABOLIC CONVERSION MIGHT BE INVOLVED IN THIS SELECTIVITY WAS PROVEN BY SEPARATE ADMIN OF GRADED DOSES OF INDIVIDUAL CARDENOLIDES TO MONARCH LARVAE, WITH SUBSEQUENT ANALYSIS OF THE CARDENOLIDE CONTENT OF THE LARVAE & ADULTS. CALACTIN & CALOTROPIN WERE STORED INTACT, BUT USCHARIDIN WAS METABOLIZED TO A MIXTURE OF CALACTIN & CALOTROPIN, WHICH WERE THE CARDENOLIDES STORED. THIS CONVERSION, A REDUCTION, OCCURRED VERY RAPIDLY DURING FEEDING, APPARENTLY IN THE GUT. REASONS OFFERED FOR THE STOREABILITY OF CALACTIN & CALOTROPIN, BUT NOT USCHARIDIN, INCL CHEMICAL INSTABILITY OF THE LATTER IN THE GUT MILIEU, POLARITY (CALACTIN & CALOTROPIN ARE MORE POLAR THAN USCHARIDIN), & THE POSSIBILITY THAT THE C-3'OH IN THE CALACTIN & CALOTROPIN WAS NEEDED FOR BINDING TO A CARRIER AND/OR TISSUE STORAGE SITE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒病例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 非人类毒性摘录

羊和牛的乳草中毒仍然是牧场主的一个问题，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、瞳孔扩张、呼吸麻痹、肠道停滞和发酵，偶尔还会出现腹泻。有时还会看到破伤风样发作。...症状可能在摄入植物的2小时后就开始出现，并可能持续数小时或数天。中毒的动物在死亡前可能会经历一段昏迷期，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 SHEEP AND 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

半数致死量(LD50)是通过使用瑞士韦伯斯特雄性小鼠对来自马利筋(一种因其对牛的毒性而知名的牛奶草)的加洛托品进行测试确定的(9.2毫克/千克，腹膜内注射)。受影响的动物变得安静且共济失调。呼吸变得急促但吃力，动物们腹部着地，四肢展开。有些颤抖，严重受影响的动物发生抽搐。小鼠给药后几分钟内出现症状；伴随阵挛性抽搐的死亡通常在1-2小时内发生。表现出中毒症状但幸存的鼠标在治疗后的几天内并未显得生病。在给药后24小时内死亡的鼠标中没有明显可见的病变。在治疗后的几天内安乐死的动物的肺中看到了出血，但这种病变的发生率并没有显著高于对照组。

...(LD50) OF...CALOTROPIN FROM ASCLEPIAS CURASSAVICA (A MILKWEED ALSO KNOWN FOR ITS TOXICITY TO CATTLE), WERE DETERMINED USING MALE SWISS WEBSTER MICE /9.2 MG/KG INTRAPERITONEAL/. ... AFFECTED ANIMALS BECAME QUIET & ATAXIC. RESPIRATION BECAME RAPID BUT LABORED, AND ANIMALS LAID FLAT ON THEIR ABDOMENS WITH THEIR LIMBS SPREAD. THERE WAS SOME TREMBLING, AND SEVERELY AFFECTED ANIMALS CONVULSED. SYMPTOMS APPEARED WITHIN A FEW MINUTES AFTER THE MICE WERE DOSED; AND DEATH, ACCOMPANIED BY CLONIC CONVULSIONS, USUALLY OCCURRED WITHIN 1-2 HR. MICE THAT EXHIBITED SYMPTOMS OF POISONING, BUT SURVIVED, DID NOT APPEAR ILL ON THE DAYS FOLLOWING TREATMENT. NO LESIONS WERE CLEARLY VISIBLE IN MICE THAT DIED WITHIN 24 HR OF BEING DOSED. HEMORRHAGES WERE SEEN IN THE LUNGS OF ANIMALS EUTHANIZED ON THE DAYS FOLLOWING TREATMENT, BUT THE INCIDENCE OF THIS LESION WAS NOT SIGNIFICANTLY GREATER THAN THE INCIDENCE IN THE CONTROL GROUP.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

对30只印度沙漠跳鼠（雄性）口服给予从Calotropis procera提取的根部（每次20毫克），每隔一天一次，持续30天，导致睾丸和附睾重量减轻，体重下降，睾丸细胞中出现嗜酸性粒细胞。睾丸染色质被破坏。睾丸、附睾和精囊中的蛋白质、唾液酸和RNA的水平显著降低。睾丸中碱性磷酸酶活性增加。血清谷丙转氨酶（SGPT）和谷草转氨酶（SGOT）活性及胆固醇水平增加。红细胞压积和血红蛋白值略有增加，而血糖和血尿素水平显著增加。

ROOT EXTRACT FROM CALOTROPIS PROCERA ADMIN ORALLY (20 MG) EVERY OTHER DAY FOR 30 DAYS TO INDIAN DESERT GERBILS (MALES, 30 ANIMALS) RESULTED IN DECR WT OF TESTIS AND EPIDIDYMIS, BODY WT DECR & PYKNOSIS IN TESTICULAR CELLS. TESTICULAR CHROMATIN WAS DESTROYED. LEVELS OF PROTEIN, SIALIC ACID AND RNA IN TESTIS, EPIDIDYMIS AND SEMINAL VESICLES WERE SIGNIFICANTLY REDUCED. ALKALINE PHOSPHATASE ACTIVITY INCR IN TESTIS. SERUM GLUTAMIC PYRUVIC TRANSAMINASE (SGPT) AND GLUTAMIC OXALOACETIC TRANSAMINASE (SGOT) ACTIVITY & CHOLESTEROL LEVELS INCR. HEMATOCRIT AND HEMOGLOBIN VALUES WERE INCR SLIGHTLY & BLOOD SUGAR AND BLOOD UREA LEVELS SIGNIFICANTLY INCR.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

当给予沙漠羊单次或多次剂量的催产素胶乳（每千克6.0至0.001毫升）口服时，会导致死亡。动物出现神经症状、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。

When Desert sheep were given single or multiple doses (6.0 to 0.001 ml/kg) of the latex of Calotropis procera orally, 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)

安全信息

• 危险等级：
  6.1(b)

反应信息

• 作为反应物：
  描述：

  牛角瓜甙 在 air 、 silica gel 作用下， 以 甲醇 、 乙醚 、 正己烷 、 异丙醇 为溶剂， 反应 0.17h， 生成 10-methoxycarbonyl-3'-epi-19-norgomphoside
  参考文献：
  名称：

  Cheung, H. T. Andrew; Nelson, Carolyn J.; Watson, Thomas R., Journal of Chemical Research, Miniprint, 1989, # 1, p. 145 - 157

  摘要：

  DOI：

文献信息

• Topical and oral formulations of cardiac glycosides for treating skin diseases
  申请人：Streeper Robert

  公开号：US20060205679A1

  公开（公告）日：2006-09-14

  The present invention provides method, preparation and use of a variety of pharmaceutical compositions containing at least one digitalis glycoside such as oleandrin, odoroside-A, neriifolin, proscillaridin-A, methyl-proscillaridin-A, digitoxin, digoxin alone or at least one digitalis glycoside complexed with cyclodextrins. In another aspect, the present invention provides an effective method to treat diseases in mammals. In yet another aspect, the present invention provides an effective method for treating skin diseases in a human or non-human animal.

  本发明提供了一种方法、制备和使用多种含有至少一种毛地黄苷类药物成分的药物组合物，例如奥利安定、奥多罗苷A、内里福林、普罗斯西拉里丁A、甲基普罗斯西拉里丁A、地高辛、地高辛或至少一种毛地黄苷类与环糊精络合的药物。另一方面，本发明提供了一种有效的方法来治疗哺乳动物的疾病。另一方面，本发明提供了一种有效的方法来治疗人类或非人类动物的皮肤疾病。
• [EN] 2" OXO-VORUSCHARIN AND DERIVATIVES THEREOF<br/>[FR] 2" OXO-VORUSCHARINE ET DERIVES DE CETTE DERNIERE
  申请人：UNIBIOSCREEN SA

  公开号：WO2004033465A1

  公开（公告）日：2004-04-22

  The present invention relates to the novel compound 2'' oxo-voruscharin and derivatives. In addition, the present invention relates to pharmaceutical compositions comprising the novel 2'' oxo-voruscharin or derivatives. The present invention further relates to the 2'' oxo-voruscharin and derivatives for use as a medicament and for use in the preparation of a medicament for treating cancer. The present invention also relates to a method of treating cancer.

  本发明涉及新型化合物2''氧代-沃鲁沙林及其衍生物。此外，本发明涉及包含新型2''氧代-沃鲁沙林或其衍生物的制药组合物。本发明还涉及将2''氧代-沃鲁沙林及其衍生物用作药物，并用于制备治疗癌症的药物。本发明还涉及一种治疗癌症的方法。
• 2''oxo-voruscharin and analogues thereof
  申请人：Unibioscreen S.A.

  公开号：EP1408043A1

  公开（公告）日：2004-04-14

  The present invention relates to the novel compound 2" oxo-voruscharin and analogues. In addition, the present invention relates to pharmaceutical compositions comprising the novel 2" oxo-voruscharin or analogues. The present invention further relates to the 2" oxo-voruscharin and analogues for use as a medicament and for use in the preparation of a medicament for treating cancer. The present invention also relates to a method of treating cancer.

  本发明涉及新型化合物 2 "氧代姜黄素及其类似物。此外，本发明还涉及包含新型 2 "氧代姜黄素或类似物的药物组合物。本发明进一步涉及用作药物和用于制备治疗癌症的药物的 2 "氧代-voruscharin 及类似物。本发明还涉及一种治疗癌症的方法。
• Method for the provision, identification and selection of proteases with altered sensitivity to activity-modulating substances
  申请人：Direvo Biotech AG

  公开号：EP1726643A1

  公开（公告）日：2006-11-29

  The present invention provides a method for the selection of proteases with altered sensitivity to one or more activity-modulating substances. The method combines the provision of a protease library encoding polynucleotide sequences, expression of the enzymes, screening of the library in the presence of one or several activity-modulating substances, selection of variants with altered sensitivity to one or several activity-modulating substances and isolation of those polynucleotide sequences that encode for the selected variants.

  本发明提供了一种选择对一种或多种活性调节物质敏感性改变的蛋白酶的方法。该方法包括提供编码多核苷酸序列的蛋白酶文库、表达酶、在一种或多种活性调节物质存在下筛选文库、选择对一种或多种活性调节物质敏感性改变的变体以及分离编码所选变体的多核苷酸序列。
• Serine proteases with altered sensitivity to activity-modulating substances
  申请人：Direvo Biotech AG

  公开号：EP2045321A2

  公开（公告）日：2009-04-08

  The present invention provides variants of serine proteases of the S1 class with altered sensitivity to one or more activity-modulating substances. A method for the generation of such proteases is disclosed, comprising the provision of a protease library encoding polynucleotide sequences, expression of the enzymes, screening of the library in the presence of one or several activity-modulating substances, selection of variants with altered sensitivity to one or several activity-modulating substances and isolation of those polynucleotide sequences that encode for the selected variants.

  本发明提供了对一种或多种活性调节物质敏感性改变的 S1 类丝氨酸蛋白酶变体。本发明公开了一种生成此类蛋白酶的方法，包括提供编码多核苷酸序列的蛋白酶文库，表达酶，在一种或多种活性调节物质存在下筛选文库，选择对一种或多种活性调节物质敏感性改变的变体，以及分离编码所选变体的多核苷酸序列。