黄曲霉毒素 | 1402-68-2

• 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 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 黄曲霉毒素
• 英文名称: aflatoxin G1
• 英文别名: 11-methoxy-6,8,16,20-tetraoxapentacyclo[10.8.0.02,9.03,7.013,18]icosa-1,4,9,11,13(18)-pentaene-17,19-dione
• CAS: 1402-68-2
• 化学式: C₁₇H₁₂O₇
• 分子量: 328.278
• InChiKey: XWIYFDMXXLINPU-UHFFFAOYSA-N

物化性质

• 物理描述：
  Solid
• 颜色/状态：
  Colorless to pale-yellow crystals
• 熔点：
  245 °C
• 溶解度：
  In water, 477 mg/L at 25 °C (est)
• 蒸汽压力：
  5.86X10-11 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Relatively unstable to light & air, particularly in soln in highly polar solvents; chloroform solutions are stable for years if kept in dark & cold.
• 旋光度：
  Specific optical rotation (chloroform): -556 deg at 25 °C/D
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 碰撞截面：
  164 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine]

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  7

ADMET

代谢

在根霉中产生黄曲霉毒素B3...在大鼠中产生黄曲霉毒素GM1。来自表格/

Yields aflatoxin B3 in rhizopus ... yields aflatoxin gm1 in rat. From table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

黄曲霉毒素B1、黄曲霉毒素B2和黄曲霉毒素G1通过静脉给药给大鼠后，迅速代谢成7组代谢物，其中6组通过胆汁排出。这三种毒素在2-和4-位置都被羟基化。接受黄曲霉毒素G1的大鼠胆汁中含有葡萄糖苷酸。

Aflatoxin B1, aflatoxin B2, & aflatoxin G1 admin iv to rats were rapidly metabolized to 7 groups of metabolites each, 6 of which were excreted in the bile. All 3 toxins were hydroxylated at the 2- & 4-positions. Bile from the rats that had received aflatoxin G1 contained glucuronide.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人类肝脏微粒体与黄曲霉毒素B1和/或黄曲霉毒素G1的孵化产生了诱导沙门氏菌typhimurium（TA-1535/psK1002）中umuC基因表达的遗传毒性代谢物。遗传毒性的效力排序是...黄曲霉毒素B1>黄曲霉毒素G1。微粒体对...黄曲霉毒素的活化在用针对p450NF的多克隆抗体孵化时被完全抑制，且在肝脏微粒体准备中p450NF（硝苯地平氧化酶）的免疫化学测定与...黄曲霉毒素G1和黄曲霉毒素B1的微粒体活化相关。P450NF在含有纯化酶和NADPH生成系统的重组单加氧酶系统中将...黄曲霉毒素转化为遗传毒性代谢物。

...The incubation of human liver microsomes with aflatoxin B1 /or/ aflatoxin G1 ...yielded genotoxic metabolites that induced umuC gene expression in Salmonella typhimurium (TA-1535/psK1002). The rank order of genotoxic potency was ...aflatoxin B1>aflatoxin G1. Microsomal activation of the ...aflatoxins was completely inhibited upon incubation with polyclonal antibodies against p450NF, and immunochemical determinations of p450NF /(nifedipine oxidase)/ in the liver microsomal preparations were correlated with the microsomal activation of ...aflatoxin G1 and aflatoxin B1. P450NF converted the ...aflatoxins to genotoxic metabolites in a reconstituted monooxygenase system containing the purified enzyme and an NADPH generating system. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

黄曲霉毒素在肝脏中通过细胞色素P-450依赖的多底物单加氧酶系统代谢为毒性较低的代谢物。黄曲霉毒素代谢的主要反应包括羟基化、氧化和脱甲基化。

Aflatoxins are metabolized in the liver by the cytochrome P-450-dependent polysubstrate mono-oxygenase system to less toxic metabolites. The main reactions in aflatoxin metabolism are hydroxylation, oxidation, and demethylation. (A2973)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

黄曲霉毒素在暴露于紫外线（365纳米）光下时会产生单线态氧。单线态氧反过来激活它们成为致突变剂和DNA结合物种。黄曲霉毒素代谢物可以通过它们的环氧基团插入DNA并烷基化碱基，特别是与N7-鸟嘌呤碱基结合。除了随机突变DNA外，这被认为会导致p53基因突变，p53是一个重要的基因，当DNA发生突变时，它能够阻止细胞周期进展或发出凋亡信号。

Aflatoxins produce singlet oxygen upon their exposure to UV (365-nm) light. Singlet oxygen in turn activates them to mutagens and DNA binding species. Aflatoxin metabolites can intercalate into DNA and alkylate the bases through their epoxide moiety, binding particularity to N7-guanine bases. In addition to randomly mutating DNA, this is thought to cause mutations in the p53 gene, an important gene in preventing cell cycle progression when there are DNA mutations, or signaling apoptosis. (L1877, A2859, A2972)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

评估：有足够的人类证据证明天然存在的黄曲霉毒素混合物具有致癌性。...有足够的实验动物证据证明天然存在的黄曲霉毒素混合物以及黄曲霉毒素B1、G1和M1具有致癌性。总体评估：天然存在的黄曲霉毒素对人类具有致癌性（第1组）。/天然存在的黄曲霉毒素/

Evaluation: There is sufficient evidence in humans for the carcinogenicity of naturally occurring mixtures of aflatoxins. ... There is sufficient evidence in experimental animals for the carcinogenicity of naturally occurring mixtures of aflatoxins and aflatoxins B1, G1 and M1. Overall evaluation: Naturally occurring aflatoxins are carcinogenic to humans (Group 1). /Naturally occurring aflatoxins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

黄曲霉毒素：已知的人类致癌物。

Aflatoxins: known to be human carcinogens. /Aflatoxins/

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：黄曲霉毒素

IARC Carcinogenic Agent:Aflatoxins

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：1类：对人类致癌

IARC Carcinogenic Classes:Group 1: Carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

黄曲霉毒素B1和G1及其代谢物以蛋白质结合物的形式存在于系统血液中。这种结合特定于血浆白蛋白，并且通过肝脏和肾脏细胞的酶促反应进行。白蛋白-黄曲霉毒素结合物是永久性的，结合是一个不可逆的过程。

Aflatoxins B1 & G1 & their metabolites exist in systemic blood as protein conjugates. This conjugation is specific to plasma albumin & proceeds enzymatically by liver & kidney cells. The albumin-aflatoxin conjugate is permanent & conjugation is an irreversible one.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

三组各四头大白母猪在怀孕和哺乳期间分别被喂食含有800 ppb纯化黄曲霉毒素B1（第1组）、800 ppb纯化黄曲霉毒素G1（第2组）或400 ppb B1和400 ppb G1（第3组）的饮食。一个对照组的四头母猪被喂食不含黄曲霉毒素的饮食。在分娩后五天和二十五天从第1组母猪的乳汁样本中发现了黄曲霉毒素B1和M1，黄曲霉毒素G1存在于第2组母猪的乳汁中，三种黄曲霉毒素都出现在第3组母猪的样本中。乳汁中黄曲霉毒素的浓度大约是饲料中的1000倍以下，但在分娩后的25天内有所增加。

Three groups of four Large White sows were fed diets containing either 800 ppb purified aflatoxin B1 (group 1), 800 ppb purified aflatoxin G1 (group 2) or 400 ppb B1 and 400 ppb G1 (group 3) throughout gestation and lactation. A control group of four sows was fed a diet free of aflatoxins. Aflatoxins B1 and M1 were found in milk samples taken five and 25 days after parturition from the sows of group 1, aflatoxin G1 was present in the milk of the sows of group 2 and all three aflatoxins were present in samples from the sows of group 3. The concentration of aflatoxin in the milk was about 1000-fold lower than that in the feed, but increased over the 25 days after parturition.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险类别：
  6.1(a)

制备方法与用途

黄曲霉毒素

黄曲霉毒素是由黄曲霉和寄生曲霉产生的有毒代谢产物，是一类含有二呋喃环和香豆素（氧杂萘邻酮）的基本结构化合物。已知分离鉴定出12种不同的黄曲霉毒素。

物理性质

• 黄曲霉毒素易溶于氯仿和甲醇，而不溶于正己烷、石油醚和乙醚。
• 在长波紫外光下产生荧光，并根据荧光颜色、RF值及结构不同命名为B1、B2、G1、G2、M1、M2、P1、R1、GM和毒醇。
• 其中，B1的产量最高，毒性最大，致癌性最强。

稳定性和热稳定性

• 黄曲霉毒素耐热，在280℃才发生裂解，一般烹调加工温度下破坏很少。
• 在中性或弱酸性溶液中非常稳定，但在pH值1~3的酸性溶液中稍分解，在pH9~10的碱性溶液中迅速分解。

污染途径

• 黄曲霉毒素主要污染粮油及其制品，如花生、花生油、玉米、大米及棉籽等。
• 国内食品检测通常以黄曲霉毒素B1作为指标，并可通过薄层层析法和高压液相色谱法进行检测。

毒性与种类 黄曲霉毒素的种类

黄曲霉毒素由黄曲霉菌（Aspergillus flavus）及寄生曲霉（A. parasilicus）产毒菌株产生，主要包含B1、B2、G1、G2及其代谢产物M1、M2、P1、B2a、G2a等。其中M1和M2是黄曲霉毒素B1和B2的衍生物。

污染途径

• 黄曲霉毒素主要污染粮油及其制品，如花生、花生油、玉米、大米、棉籽等。
• 除食品外，核桃、杏仁、榛子、高粱、小麦、黄豆及豆类、马铃薯、蛋、乳及乳制品、肝、香肠或鱼干及辣椒等也可能受到污染。

地区差异

在南方高温、高湿地区，一些粮油及其制品容易受黄曲霉毒素污染。而在华北、东北和西北地区，除了个别样品外，通常不会受到黄曲霉毒素的污染。

危险性分类

• 类别：有毒物品。
• 毒性分级：剧毒。
• 急性毒性
  • 口服（人）LD50：0.229毫克/公斤
  • 口服（猴子）LD50：1.75毫克/公斤
• 可燃性危险特性：可燃；燃烧时释放刺激烟雾。
• 储运特性：库房需通风、低温干燥，与食品原料分开存放。
• 灭火剂：干粉、泡沫、砂土、二氧化碳及雾状水。

反应信息

• 作为产物：
  描述：

  (+/-)-O-methylsterigmatocystin 生成 黄曲霉毒素
  参考文献：
  名称：

  YABE, K.;ANDO, Y.;TERAKADO, N.;HASHIMOTO, J.;NAKAJIMA, H.;HAMASAKI, T., MYCOTOXINS AND PHYCOTOXINS88: COLLECT INVIT. PAP. 7TH INT. IUPAC SYMP., T+

  摘要：

  DOI：

文献信息

• Drug Resistance Reversal In Neoplastic Disease
  申请人：Patil Ghanshyam

  公开号：US20080200405A1

  公开（公告）日：2008-08-21

  The present invention is directed to compounds, compositions, and methods for halting or reversing the effects of chemoresistance in neoplastic diseases. In particular the use of hydroxylamines is described.

  本发明涉及用于阻止或逆转肿瘤性疾病化疗耐药效应的化合物、组合物和方法。具体描述了羟胺的使用。
• [EN] HUMANIZED ANTI-TN-MUC1 ANTIBODIES AND THEIR CONJUGATES<br/>[FR] ANTICORPS ANTI-TN-MUC1 HUMANISÉS ET LEURS CONJUGUÉS
  申请人：CANCER REC TECH LTD

  公开号：WO2015159076A1

  公开（公告）日：2015-10-22

  Humanized anti-Tn-MUC1 antibodies and conjugates thereof. Conjugates comprising pyrrolobenzodiazepines (PBDs) having a labile protecting group in the form of a linker to the antibody are described.

  人性化抗Tn-MUC1抗体及其结合物。描述了包含吡咯苯并二氮杂环己烷（PBDs）的结合物，其具有作为连接物的不稳定保护基团。
• RAD51 Inhibitors
  申请人：Cyteir Therapeutics, Inc.

  公开号：US20190077799A1

  公开（公告）日：2019-03-14

  This application is directed to inhibitors of RAD51 represented by the following structural formula, and methods for their use, such as to treat cancer, autoimmune diseases, immune deficiencies, or neurodegenerative diseases.

  这个应用程序是针对由以下结构式代表的RAD51抑制剂，以及它们的使用方法，例如用于治疗癌症、自身免疫疾病、免疫缺陷或神经退行性疾病。
• METHODS OF USING RAD51 INHIBITORS FOR TREATMENT OF PANCREATIC CANCER
  申请人：Cyteir Therapeutics, Inc.

  公开号：US20200397760A1

  公开（公告）日：2020-12-24

  This application is directed to inhibitors of RAD51 represented by the following structural formula, and methods for their use, such as to treat pancreatic cancer.

  这个应用程序是针对由以下结构式代表的RAD51抑制剂，以及它们的使用方法，例如用于治疗胰腺癌。
• [EN] SMALL MOLECULES AGAINST CEREBLON TO ENHANCE EFFECTOR T CELL FUNCTION<br/>[FR] PETITES MOLÉCULES DIRIGÉES CONTRE LE CÉRÉBLON POUR AMÉLIORER LA FONCTION DES LYMPHOCYTES T EFFECTEURS
  申请人：H LEE MOFFITT CANCER CENTER & RES INST INC

  公开号：WO2017161119A1

  公开（公告）日：2017-09-21

  Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.

  披露了针对小脑蛋白以增强效应T细胞功能的小分子。还披露了制造这些分子的方法以及使用它们治疗各种疾病状态的方法。

表征谱图