Gyromitrin | 61748-06-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: Gyromitrin
• 英文别名: N-[(E)-ethylideneamino]-N-methylformamide
• CAS: 61748-06-9；16568-02-8
• 化学式: C₄H₈N₂O
• 分子量: 100.12
• InChiKey: IMAGWKUTFZRWSB-HWKANZROSA-N

物化性质

• 沸点：
  187.56°C (rough estimate)
• 密度：
  1.1275 (rough estimate)
• 溶解度：
  氯仿（可溶）、DMSO（少量溶解）、乙酸乙酯（少量溶解）
• LogP：
  -0.300 (est)
• 颜色/状态：
  COLORLESS LIQ
• 熔点：
  19.5 °C (VACUUM)
• 稳定性/保质期：
  VERY SENSITIVE TO AIR OXIDATION; SENSITIVE TO HYDROLYSIS BY BOTH ACIDS AND ALKALIS

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

N-甲基-N-甲酰肼，由 gyrmitrin 经水解形成，在大鼠应用后可降低肝微粒体中的细胞色素 P450 浓度。这种降低可以通过用苯巴比妥预处理大鼠来加强，但不会被 3-甲基胆蒽诱导。细胞色素 P450 介导的甲基甲酰肼氧化成羟基胺衍生物，进而形成亚硝胺，与其生物活性的重要性相关，本文对此进行了讨论。这种亚硝胺的形成可能是已知甲基甲酰肼具有肝致癌性的原因。

N-METHYL-N-FORMYLHYDRAZINE, FORMED BY HYDROLYSIS FROM GYROMITRIN, LOWERS THE CYTOCHROME P450 CONCN IN LIVER MICROSOMES AFTER ITS APPLICATION TO RATS. THIS DECR CAN BE INTENSIFIED BY PRETREATMENT OF THE RATS WITH PHENOBARBITAL BUT NOT BY INDUCTION WITH 3-METHYLCHOLANTHRENE. THE CYTOCHROME P450 MEDIATED OXIDATION OF METHYLFORMYLHYDRAZINE TO A HYDROXYLAMINE DERIVATIVE AND FURTHER TO A NITROSAMIDE, IS DISCUSSED IN RELATION TO ITS IMPORTANCE FOR THE BIOLOGICAL ACTION OF THE HYDRAZINE. THIS NITROSAMIDE FORMATION MAY BE THE REASON FOR THE KNOWN HEPATOCARCINOGENICITY OF METHYLFORMYLHYDRAZINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在37°C下，模拟人类胃部环境的条件下，不同酸性条件下，gyromitrin会转化为甲基肼，后者在小鼠和仓鼠中是一种已知的肿瘤诱导剂，通过一个中间产物N-甲基-N-甲酰肼。在小鼠口服给予gyromitrin后，其胃部也会形成甲基肼。

@ 37 °C UNDER DIFFERENT ACIDIC CONDITIONS, MIMICKING THE MILIEU OF HUMAN STOMACH, GYROMITRIN IS CONVERTED TO METHYLHYDRAZINE, A KNOWN TUMOR INDUCER IN MICE AND HAMSTERS, THROUGH AN INTERMEDIATE, N-METHYL-N-FORMYLHYDRAZINE. METHYLHYDRAZINE IS ALSO FORMED IN THE MOUSE STOMACH AFTER ORALLY ADMIN OF GYROMITRIN.

来源:Hazardous Substances Data Bank (HSDB)

代谢

N-甲基-N-甲酰肼是蘑菇毒肽基罗米亭的第一个活性中间体：假羊肚菌。这种化合物是人类肠道二胺氧化酶的非竞争性抑制剂（ID50 = 1.6 X 10(-5) mol/l）。这个浓度相当于每升蘑菇湿重不到5克。来自其他5个来源的二胺氧化酶以类似的方式被抑制。氨甲酰和胍胺分别是人类肠道二胺氧化酶的10倍和1000倍更强的抑制剂。考虑到N-甲基-N-甲酰肼对人类肠道二胺氧化酶抑制性质在物质的毒性和致突变效果中的作用。

N-methyl-N-formylhydrazine is the first active intermediate of the poison gyromitrin of the mushroom: false morel. This compound is a non-competitive inhibitor of human intestinal diamine oxidase (ID50 = 1.6 X 10( -5 ) mol/l) . This concn corresponds to less than 5 g of wet weight of mushroom/l. The diamine oxidases from 5 other sources are inhibited in a similar manner. Semicarbazide and aminoguanidine are 10-respectively 1000-fold more potent inhibitors of the human intestinal diamine oxidase. An involvement of the diamine oxidase inhibitory property of N-methyl-N-formylhydrazine in toxic and mutagenic effects of the substance is considered.

来源:Hazardous Substances Data Bank (HSDB)

代谢

单甲基肼（MMH）和不对称二甲肼（UDMH），但不是N-甲基-N-甲酰肼（MFH），一种蘑菇毒素，可以被弱氧化剂6-二氯酚靛酚氧化。这种氧化过程中形成了过氧化氢，并且发现它能在水溶液中导致DNA的降解，这是通过测量在肼存在下DNA溶液的粘度降低来确定的。此外，MMH和UDMH但不是MFH抑制了(3)H-胸苷和(3)H-尿苷掺入艾氏腹水癌（EAC）的DNA和RNA中。这些实验表明，MFH是一种活性较低的化合物，与MMH和UDMH相反。由于MFH水解生成MMH的速率较低，因此可以推断MFH在体内必须转化为有毒的代谢物，这些代谢物最终负责MFH已知的高致癌性。

Monomethylhydrazine (MMH) and unsymmetrical dimethylhydrazine (UDMH), but not N-methyl-N-formylhydrazine (MFH), a mushroom poison, can be oxidized by the weak oxidant 6-dichlorophenolindophenol. Hydrogen peroxide is formed by this oxidation, and has been found to cause decay of DNA in aqueous solution as measured by the decr viscosity of a DNA solution the presence of the hydrazines. Furthermore, MMH and UDMH but not MFH inhibit the incorporation of (3)H-thymidine and (3)H-uridine into DNA and RNA of Ehrlich ascites carcinoma (EAC). These experiments show that MFH is an inactive compound in contrast to MMH and UDMH. Since the hydrolysis rate of MFH, to induce MMH, is low, it is concluded that MFH must be activated vivo into toxic metabolites which are ultimately responsible the known high carcinogenicity of MFH.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝毒性及致癌性的N-甲基-N-甲酰肼（MFH），是由蘑菇毒素蝇蕈碱通过体内和体外食物加工过程中的水解裂解形成的，在自由氨基团上乙酰化后，其对大鼠的肝毒性和对肾功能的影响会丧失。考虑到MFH乙酰化对抑制微囊体转化MFH为有毒亚硝酰胺的重要性。人类对肼衍生物乙酰化速率的遗传决定性异质性，可能解释了对蘑菇毒素敏感性观察到的差异。

The hepatotoxic and cancerogenic N-methyl-N-formyl hydrazine (MFH), which is formed from the mushroom poison gyromitrin, by hydrolytic cleavage in vivo and in vitro during food processing, loses its hepatotoxicity and its influence on the renal function of rats after acetylation at the free NH2-moiety. The importance of MFH-acetylation with regard to an inhibition of microsomal conversion of MFH into a toxic nitrosamide is considered. The known genetically determined heterogeneity of the acetylation rate for hydrazine derivatives in man may explain the observed differences in sensitivity towards the mushroom toxins.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。动物致癌性证据有限。总体评估：第3组：该物质对人类致癌性无法分类。

No data are available in humans. Limited evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.

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：gyromitrin（毒伞素）

IARC Carcinogenic Agent:Gyromitrin

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：无法归类其对人类致癌性

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著：第31卷：（1983年）某些食品添加剂、饲料添加剂和天然存在物质

IARC Monographs:Volume 31: (1983) Some Food Additives, Feed Additives and Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素 职业性肝毒素 - 继发性肝毒素：职业环境中潜在毒性效应的判断基于人类摄入或动物实验的中毒案例。 溶血性贫血 - 血红蛋白或红细胞数量减少。

Neurotoxin - Other CNS neurotoxin 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. Hemolytic anemia - Decreased hemoglobin or number of red blood cells.

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

吸收、分配和排泄

乙基亚硝基甘油的急性口服毒性在兔、大鼠和鸡上进行测定。兔子至少将一部分未改变的乙基亚硝基甘油通过尿液排出。

THE ACUTE ORAL TOXICITY OF ETHYLIDENE GYROMITRIN WAS DETERMINED IN RABBITS, RATS AND CHICKENS. RABBITS EXCRETED AT LEAST PART OF THE ADMIN ETHYLIDENE GYROMITRIN UNCHANGED IN THE URINE.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)

制备方法与用途

类别：有毒物质
毒性分级：高毒
急性毒性：口服-大鼠 LD50: 320毫克/公斤；口服-小鼠 LD50: 344毫克/公斤
可燃性危险特性：可燃；加热分解释放有毒氮氧化物烟雾
储运特性：库房通风、低温干燥
灭火剂：水、二氧化碳、干粉、砂土