节球毒素 | 118399-22-7

• 物质功能分类: 分析化学 - 标准品 - 食品和化妆品标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 节球毒素
• 中文别名: 环[(2S,3S,4E,6E,8S,9S)-3-氨基-9-甲氧基-2,6,8-三甲基-10-苯基-4,6-癸二烯酰基-D-Γ-谷氨酰基-(2Z)-2-(甲氨基)-2-丁烯酰基-(3S)-3-甲基-DΒ-天冬氨酰-L-精氨酰)
• 英文名称: nodularin
• 英文别名: nodularin R；NOD；(2Z,5R,6S,9S,12S,13S,16R)-9-[3-(diaminomethylideneamino)propyl]-2-ethylidene-12-[(1E,3E,5S,6S)-6-methoxy-3,5-dimethyl-7-phenylhepta-1,3-dienyl]-1,6,13-trimethyl-3,7,10,14,19-pentaoxo-1,4,8,11,15-pentazacyclononadecane-5,16-dicarboxylic acid
• CAS: 118399-22-7
• 化学式: C₄₁H₆₀N₈O₁₀
• 分子量: 824.975
• InChiKey: IXBQSRWSVIBXNC-HSKGSTCASA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)
• 闪点：
  11℃
• 溶解度：
  在甲醇中可溶2 mg/mL 进一步稀释至 10% (v/v) 甲醇。在“20”C 下储存解决方案长达六个月。
• 分解：
  Hazardous Decomposition Products: Carbon monoxide, carbon dioxide.
• 聚合：
  Hazardous Polymerization: Will not occur.
• 碰撞截面：
  300.71 Ų [M+H]+

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  59
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  285
• 氢给体数：
  8
• 氢受体数：
  11

ADMET

代谢

蓝藻毒素微囊藻毒素-LR（MCLR）、Dhb-微囊藻毒素-HtyR和结节藻毒素在盐水虾阿拉米亚萨利纳的卵囊、无节幼体和成体中的毒性和代谢进行了研究。这些阶段中存在II期解毒系统谷胱甘肽S-转移酶（sGST），使用不同的底物进行了展示。成年A. salina暴露于毒素导致体内GST活性升高。所有三种毒素都通过GST与谷胱甘肽结合，这已被证明是微囊藻毒素和结节藻毒素解毒的初始步骤。

The toxicity and metabolism of the cyanobacterial toxins microcystin-LR (MCLR), Dhb-microcystin-HtyR and nodularin were investigated in the cysts, nauplii and adults of the brine shrimp Artemia salina. The presence of the phase II detoxication system glutathione S-transferase (sGST) in these stages was shown using different substrates. Exposure of adult A. salina to the toxins led to an elevation of GST activity in vivo. All three toxins were conjugated to glutathione via GST, which has been shown as an initial step of microcystin and nodularin detoxication.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

对于人类而言，结节藻毒素的致癌性证据不足……在实验动物中，结节藻毒素的致癌性证据也不足。总体评估：……结节藻毒素对人类的致癌性无法分类（第3组）。

There is inadequate evidence in humans for the carcinogenicity of nodularins ... There is inadequate evidence in experimental animals for the carcinogenicity of nodularins. Overall evaluation: ... Nodularins are not classifiable as to their carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：结节性毒素

IARC Carcinogenic Agent:Nodularins

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：对其对人类的致癌性无法分类

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专论：第94卷：（2010年）摄入的硝酸盐和亚硝酸盐以及蓝藻肽毒素

IARC Monographs:Volume 94: (2010) Ingested Nitrate and Nitrite, and Cyanobacterial Peptide Toxins

来源:International Agency for Research on Cancer (IARC)

毒理性

• 相互作用

结节素和微囊藻毒素-LR是蓝藻毒素，也是环境的危害。结节素对蛋白磷酸酶1和2A的抑制能力与微囊藻毒素-LR相当，后者最近被识别为大鼠肝脏的一种强效肿瘤促进剂。在雄性F344大鼠肝脏进行的一个两阶段致癌实验中，使用二乙基亚硝胺启动，且没有进行部分肝切除，结果显示结节素比微囊藻毒素-LR更有效地刺激大鼠肝脏中谷胱甘肽S-转移酶胎盘形式阳性焦点的形成，并且结节素单独诱导谷胱甘肽S-转移酶胎盘形式阳性焦点的效果与二乙基亚硝胺单独作用相当。因此，结节素本身是一种新的肝脏致癌物，而微囊藻毒素-LR是一种肿瘤促进剂，而不是致癌物。结节素在原代培养的大鼠肝细胞中诱导细胞角蛋白肽8和18的超磷酸化比微囊藻毒素-LR高出20%，这表明结节素比微囊藻毒素-LR更容易渗透进入肝细胞。结节素在腹腔注射后上调了大鼠肝脏中c-jun、jun-B、jun-D、c-fos、fos-B和fra-1 mRNA转录本的诱导，并且在处理后9小时以上，这些mRNA转录本的积累仍然持续。本文讨论了蓝藻毒素的环境危害与中华人民共和国启东县人类原发性肝癌的关系...

Nodularin and microcystin-LR are cyanobacterial toxins and environmental hazards. Nodularin inhibits protein phosphatases 1 and 2A with the same potency as does microcystin-LR, which has recently been identified as a potent tumor promoter in rat liver. ... A two-stage carcinogenesis experiment in /male F344/ rat liver initiated with diethylnitrosamine and without partial hepatectomy revealed that nodularin stimulated glutathione S-transferase placental form-positive foci in rat liver more effectively than did microcystin-LR, and that nodularin alone induced glutathione S-transferase placental form-positive foci as well as did diethylnitrosamine alone. Thus, nodularin itself is a new liver carcinogen, and microcystin-LR is a tumor promoter rather than a carcinogen. Nodularin induced hyperphosphorylation of cytokeratin peptides 8 and 18 in primary cultured rat hepatocytes 20% more effectively than did microcystin-LR, suggesting that nodularin penetrates more easily into the hepatocytes than does microcystin-LR. Nodularin up-regulated induction of c-jun, jun-B,jun-D,c-fos,fos-B, and fra-1 mRNA transcripts in rat liver after i.p. administration, and the accumulation of the mRNA transcripts was sustained for over 9 hr after treatment. The environmental hazards of cyanobacterial toxins are discussed in relation to human primary liver cancer in Qidong county in the People's Republic of China...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...结节素被标记上放射性同位素(125)I，然后通过口服、腹腔注射和静脉注射给小鼠。通过放射性同位素和自动放射性显影技术研究了结节素在靶器官的分布和结节素的细胞定位。...结节素在小鼠体内主要分布在肾脏和肝脏中。进一步的自动放射性显影研究表明，结节素分布在肾细胞核和肝细胞核中...

... Nodularin was labeled with radioactive isotope (125)I and then was given to mice via oral, intraperitoneal and intravenous administration. The distribution of nodularin in target organs and the cellular location of nodularin were studied by radioisotope and autoradiography techniques. ... Nodularin was mainly distributed in the kidney and liver in mice. Further autoradiography study indicated that nodularin was distributed in the renal cell nuclei and liver cell nuclei...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  T+,F,T
• 安全说明：
  S16,S26,S36/37,S36/37/39,S45,S7
• 危险类别码：
  R38,R36/37/38,R43,R26/27/28,R11,R23/24/25,R39/23/24/25
• WGK Germany：
  1,3
• 危险品运输编号：
  UN 2811 6.1/PG 2

SDS

节球毒素MSDS英文版

反应信息

• 作为反应物：
  描述：

  节球毒素 生成 甲胺
  参考文献：
  名称：

  RINEHART, KENNETH L.;HARADA, KEN-ICHI;NAMIKOSHI, MICHIO;CHEN, CHORYU;HARV+, J. AMER. CHEM. SOC., 110,(1988) N 25, C. 8557-8558

  摘要：

  DOI：
• 作为产物：
  描述：

  Nod-AM2 在 pig liver esterase 作用下， 生成 节球毒素
  参考文献：
  名称：

  Acyloxymethyl Esterification of Nodularin-R and Microcystin-LA Produces Inactive Protoxins that Become Reactivated and Produce Apoptosis inside Intact Cells

  摘要：

  We report the esterification of the carboxyl groups of the cyclic peptide toxins nodularin-R. and microcystin-LA to produce stable diacetoxymethyl and dipropionyloxymethyl ester derivatives. The derivatives had no activity but were reactivated upon esterase treatment. When injected into cells, the acyloxymethyl moieties were cleaved off and apoptosis induced. Linking the acyloxymethyl-ester moiety of these potent toxins to carriers destined for endocytosis paves the way for selective apoptosis induction in target (e.g., cancer) cells.

  DOI：

  10.1021/jm900502e

文献信息

• Total synthesis of Adda, the unique C20 amino acid of cyanobacterial hepatotoxins
  作者：Michio Namikoshi、Kenneth L. Rinehart、Andrew M. Dahlem、Val R. Beasley、Wayne W. Carmichael

  DOI：10.1016/s0040-4039(00)99357-2

  日期：1989.1
• RINEHART, KENNETH L.;HARADA, KEN-ICHI;NAMIKOSHI, MICHIO;CHEN, CHORYU;HARV+, J. AMER. CHEM. SOC., 110,(1988) N 25, C. 8557-8558
  作者：RINEHART, KENNETH L.、HARADA, KEN-ICHI、NAMIKOSHI, MICHIO、CHEN, CHORYU、HARV+

  DOI：——

  日期：——
• Methods And Kits For The Determining The Presence Or Absence Of Cyanobacteria Toxins
  申请人：Oehrle Stuart A.

  公开号：US20110269241A1

  公开（公告）日：2011-11-03

  Embodiments of the present invention are directed to kits and methods for the detection of toxins produced by cyanobacteria. The methods and kits feature sample preparation steps with weak cationic and anionic exchange resins and small particle analytical columns operating at 4,000 to 15,000 psi.
• Acyloxymethyl Esterification of Nodularin-R and Microcystin-LA Produces Inactive Protoxins that Become Reactivated and Produce Apoptosis inside Intact Cells
  作者：Lars Herfindal、Franciszek Kasprzykowski、Frank Schwede、Leszek L̷ankiewicz、Kari E. Fladmark、Joanna L̷ukomska、Matti Wahlsten、Kaarina Sivonen、Zbigniew Grzonka、Bernd Jastorff、Stein Ove Do̷skeland

  DOI：10.1021/jm900502e

  日期：2009.9.24

  We report the esterification of the carboxyl groups of the cyclic peptide toxins nodularin-R. and microcystin-LA to produce stable diacetoxymethyl and dipropionyloxymethyl ester derivatives. The derivatives had no activity but were reactivated upon esterase treatment. When injected into cells, the acyloxymethyl moieties were cleaved off and apoptosis induced. Linking the acyloxymethyl-ester moiety of these potent toxins to carriers destined for endocytosis paves the way for selective apoptosis induction in target (e.g., cancer) cells.