雪卡鱼毒素 | 11050-21-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 雪卡毒素
• 中文名称: 雪卡鱼毒素
• 英文名称: CTX1B
• 英文别名: Ciguatoxin；Pacific ciguatoxin 1；(1R,3S,3'S,6R,8S,10R,12S,16R,18R,19R,20S,22R,25S,27R,29Z,32S,34R,36S,38R,40S,42R,43S,44S,45R,47S,48S,49S,50R,52S,54R,56R,58S,59R)-16-[(E,3S)-3,4-dihydroxybut-1-enyl]-43,44,49,54,58-pentamethylspiro[2,7,11,17,21,26,33,37,41,46,51,57-dodecaoxadodecacyclo[30.28.0.03,27.06,25.08,22.010,20.012,18.034,58.036,56.038,52.040,50.042,47]hexaconta-4,14,23,29-tetraene-45,5'-oxolane]-3',19,48,59-tetrol
• CAS: 11050-21-8
• 化学式: C₆₀H₈₆O₁₉
• 分子量: 1111.33
• InChiKey: VYVRIXWNTVOIRD-LRHBOZQDSA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)
• 颜色/状态：
  White solid

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  79
• 可旋转键数：
  3
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  241
• 氢给体数：
  6
• 氢受体数：
  19

ADMET

毒理性

• 毒性总结

雪卡毒素降低了神经系统突触中开启电压门控钠通道的阈值。打开钠通道的效果将导致去极化，这可能会依次导致瘫痪、心脏收缩以及改变听觉和冷感。因为它不穿过血脑屏障（BBB），雪卡毒素只影响周围神经系统（PNS）。(L994, A301)

Ciguatoxin lowers the threshold for opening voltage-gated sodium channels in synapses of the nervous system. The effect of opening a sodium channel will cause depolarization, which could sequentially cause paralysis, heart contraction, and changing the senses of hearing and cold. Because it does not cross the blood brain barrier (BBB), ciguatoxins solely affect the peripheral nervous system (PNS). (L994, A301)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

雪卡毒素中毒会导致麻痹、心脏收缩以及听力和寒冷感觉的改变。因为它不能穿过血脑屏障（BBB），雪卡毒素只影响周围神经系统（PNS）（L994）。

Ciguatoxin poisoning can cause paralysis, heart contraction, and changing the senses of hearing and cold. Because it does not cross the blood brain barrier (BBB), ciguatoxins solely affect the peripheral nervous system (PNS) (L994).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服（A300）

Oral (A300)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

主要症状将在摄入毒素后几小时内出现：呕吐、腹泻、四肢、口和嘴唇麻木、冷热感觉颠倒、肌肉和关节疼痛。症状可能持续几天到几周甚至几个月，具体取决于每个人的情况（A325）。

The major symptoms will develop just a few hours of toxin ingestion: vomiting, diarrhea, numbness of extremities, mouth and lips, reversal of hot and cold sensation, muscle and joint aches. The symptoms may last from days to weeks or even months depending on each individual situation (A325).

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

在这项研究中，研究人员确定了太平洋雪卡毒素P-CTX-1在大鼠体内的毒物动力学参数，在大鼠体内静脉注射(iv)0.13 ng P-CTX-1每克体重后。随着时间的推移，使用敏感的功能性Neuro2a检测法在血液中评估了雪卡毒素的活性。数据使用双室模型进行分析。暴露后，雪卡毒素活性表现出迅速（alpha半衰期为6分钟）并广泛分布到组织中（表观稳态分布体积为7.8 L）。血液中雪卡毒素的消除较慢，beta半衰期估计为35.5小时。从这项研究中确定的毒物动力学参数与之前在大鼠口服和腹腔注射0.26 ng P-CTX-1每克体重后获得的数据进行了比较。最大生物利用度由浓度曲线下的面积确定，并用于计算口服和腹腔注射暴露途径的绝对P-CTX-1生物利用度分别为39%和75%。

In this study, /the researchers/ determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0.13 ng P-CTX-1 per g of body weight. The ciguatoxin activity was assessed over time in blood using the sensitive functional Neuro2a assay. The data were analyzed with a two-compartmental model. After exposure, the ciguatoxin activity exhibited a rapid (alpha half-life of 6 min) and extensive distribution into tissues (apparent steady state volume of distribution of 7.8 L). Ciguatoxin elimination from blood was slower with a beta half-life estimated at 35.5 hr. The toxicokinetic parameters determined from this study were compared to data previously obtained after oral and intraperitoneal exposure of rats to 0.26 ng P-CTX-1 per g of body weight. Maximal bioavailability was determined by the area under the concentration curve, and was used to calculate the absolute P-CTX-1 bioavailabilities for oral and intraperitoneal routes of exposures of 39% and 75%, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雪卡毒素在所有鱼的组织中积累，尤其是在“有风险”物种的肝脏和内脏中。

Ciguatoxin accumulates in all fish tissues, especially the liver and viscera, of "at risk" species.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雪卡毒素在人类中通常是由食用积累了雪卡毒素（CTXs）的珊瑚礁鱼类引起的。在六个月的时间里，研究人员捕获了38条野生成年大梭鱼（Sphyraena barracuda），这种鱼在巴哈马与雪卡病有关。研究人员采集了三种组织（即肌肉、肝脏和血液）的样本，并使用功能性的体外N2A生物测定法分析了雪卡毒素的存在。在三种组织类型中发现的可检测浓度的雪卡毒素从2.51到211.74pg C-CTX-1当量/克不等。血液和肝脏毒素浓度呈正相关（P=0.86，P=0.003），这表明...血液采样提供了一种非致命的检测野生鱼类中雪卡毒素的方法。非致命的血液采样还为将这种方法与生物遥测和生物记录技术相结合提供了机会，这些技术使得研究鱼类的分布和移动成为可能。为了证明将雪卡毒素发生与梭鱼空间生态学联系起来的潜力，研究人员还展示了一个概念验证案例研究，其中从20条鱼中采集血液样本，然后释放它们，并使用固定声学遥测阵列跟踪它们在44平方公里范围内的沿海水域。检测出CTX阳性的鱼类可能比无毒鱼类的活动范围小（中位行驶距离，U=2.21，P=0.03）。本研究展示的结果可能有助于识别高风险区域和毒素的源汇动态，从而可能降低雪卡鱼中毒的发病率和人类健康风险。此外，非致命采样方法的开发和从血液中测量雪卡毒素为未来理解毒素与广泛海洋鱼类物种的空间生态学之间的机制关系提供了机会。

Ciguatera in humans is typically caused by the consumption of reef fish that have accumulated Ciguatoxins (CTXs) in their flesh. Over a six month period, /the researchers/ captured 38 wild adult great barracuda (Sphyraena barracuda), a species commonly associated with ciguatera in The Bahamas. /The researchers/ sampled three tissues (i.e., muscle, liver, and blood) and analysed them for the presence of ciguatoxins using a functional in vitro N2A bioassay. Detectable concentrations of ciguatoxins found in the three tissue types ranged from 2.51 to 211.74pg C-CTX-1 equivalents/g. Blood and liver toxin concentrations were positively correlated (P=0.86, P=0.003), indicating that ... blood sampling provides a non-lethal method of detecting ciguatoxin in wild fish. Non-lethal blood sampling also presents opportunities to couple this approach with biotelemetry and biologging techniques that enable the study of fish distribution and movement. To demonstrate the potential for linking ciguatoxin occurrence with barracuda spatial ecology, /the researchers/ also present a proof-of-concept case study where blood samples were obtained from 20 fish before releasing them with acoustic transmitters and tracking them in the coastal waters using a fixed acoustic telemetry array covering 44km(2). Fish that tested positive for CTX may have smaller home ranges than non-toxic fish (median distance travelled, U=2.21, P=0.03). Results presented from this study may help identify high risk areas and source-sink dynamics of toxins, potentially reducing the incidence and human health risk of ciguatera fish poisoning. Moreover, development of the non-lethal sampling approach and measurement of ciguatera from blood provide future opportunities to understand the mechanistic relationship between toxins and the spatial ecology of a broad range of marine fish species.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雪卡毒素也可以通过母乳传播，并且能够穿过胎盘影响胎儿。

Ciguatoxins are also transmitted in breast milk and are able to cross the placenta and affect the fetus.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

类别：有毒物质

毒性分级：剧毒

急性毒性：

• 静脉注射大鼠 LD50: 11 毫克/公斤
• 腹腔注射小鼠 LD50: 0.25 毫克/公斤

可燃性危险特性：可燃，燃烧时分解产生有毒的氮氧化物气体

储运特性：

• 库房应保持低温、通风和干燥
• 需与食品原料分开存放

灭火剂：

• 水
• 二氧化碳
• 干粉
• 砂土

反应信息

• 作为产物：
  描述：

  (1R,3S,3'S,6R,8S,10R,12S,16R,18R,19R,20S,22R,25S,27R,29Z,32S,34R,36S,38R,40S,42R,43S,44S,45R,47S,48S,49S,50R,52S,54R,56R,58S,59R)-43,44,49,54,58-pentamethyl-16-[(E)-2-[(4S)-2-naphthalen-2-yl-1,3-dioxolan-4-yl]ethenyl]spiro[2,7,11,17,21,26,33,37,41,46,51,57-dodecaoxadodecacyclo[30.28.0.03,27.06,25.08,22.010,20.012,18.034,58.036,56.038,52.040,50.042,47]hexaconta-4,14,23,29-tetraene-45,5'-oxolane]-3',19,48,59-tetrol 在 盐酸 、 甲醇 、 水 作用下， 反应 0.5h， 生成 雪卡鱼毒素
  参考文献：
  名称：

  METHOD OF SYNTHESIS OF CIGUATOXIN CTX1B AND COMPOUNDS USEFUL FOR THE SYNTHESIS OF CIGUATOXIN CTX1B

  摘要：

  公开号：

  EP1982988B1

文献信息

• METHOD FOR SYNTHESIS OF CIGUATOXIN CTX1B AND COMPOUNDS USEFUL FOR THE SYNTHESIS OF CIGUATOXIN CTX1B
  申请人：Hirama Masahiro

  公开号：US20100160651A1

  公开（公告）日：2010-06-24

  Disclosed is a method for total synthesis of CTX1B, which is developed for the synthesis of a ciguatoxin analogue such as CTX3C and enables the more efficient application of an established reaction to the total synthesis of CTC1B. More specifically, disclosed is a method for total synthesis of CTX1B comprising; an 0.5-acetal formation for synthesizing a novel compound (3); a radical cyclization reaction for constructing a 9-membered ring formation reaction including a novel compound (6) through a novel compound (8) and yielding a compound (D); and a deprotection for yielding CTX1B. Also disclosed are novel compounds (1) to (8) which are particularly useful for synthesis of CTX1B and can be used for the synthesis of a ciguatoxin analogue.
• Ladder-Frame Polyether Conjugates
  申请人：CAROLINA AT WILMINGTON UNIVERSITY OF NORTH

  公开号：US20140073604A1

  公开（公告）日：2014-03-13

  Disclosed are compounds that are conjugates of ladder frame polyether compounds and biologically active compounds or research compounds, pharmaceutical formulations comprising the conjugates, and methods of transporting the conjugates across biological membranes.
• METHOD OF SYNTHESIS OF CIGUATOXIN CTX1B AND COMPOUNDS USEFUL FOR THE SYNTHESIS OF CIGUATOXIN CTX1B
  申请人：Japan Science and Technology Agency

  公开号：EP1982988B1

  公开（公告）日：2014-06-04