(1R,6aS,9aS)-1-hydroxy-4-(methyloxy)-2,3,6a,9a-tetrahydrocyclopenta[c]furo[3',2':4,5]furo[2,3-h]chromen-11(1H)-one | 29611-03-8

• 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
• 英文名称: (1R,6aS,9aS)-1-hydroxy-4-(methyloxy)-2,3,6a,9a-tetrahydrocyclopenta[c]furo[3',2':4,5]furo[2,3-h]chromen-11(1H)-one
• 英文别名: (3S,7S,16R)-16-hydroxy-11-methoxy-6,8,19-trioxapentacyclo[10.7.0.02,9.03,7.013,17]nonadeca-1,4,9,11,13(17)-pentaen-18-one
• CAS: 29611-03-8
• 化学式: C₁₇H₁₄O₆
• 分子量: 314.29
• InChiKey: WYIWLDSPNDMZIT-BTKFHORUSA-N

物化性质

• 熔点：
  225°C
• 沸点：
  373.98°C (rough estimate)
• 密度：
  1.2564 (rough estimate)
• 溶解度：
  甲醇：1mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

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光（365纳米）时会生成单线态氧。单线态氧反过来激活它们成为诱变剂和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基因的突变，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

• 致癌物分类

未直接列入国际癌症研究机构(IARC)名单。黄曲霉毒素B1对人类具有致癌性（第1组）。

Not directly listed by IARC. Aflatoxin B1 is carcinogenic to humans (Group 1). (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

在哺乳动物中，黄曲霉毒素的主要靶器官是肝脏，因此黄曲霉毒素中毒主要是一种肝脏疾病。长期暴露于黄曲霉毒素可能会导致肝脏损伤和坏死、胆汁淤积以及肝细胞瘤。此外，长期暴露于黄曲霉毒素与肝细胞癌、急性肝炎、雷耶综合症、胆管细胞增生、门脉周围纤维化、出血、粘膜黄疸、脂肪肝变化、营养不良儿童的肝硬化以及恶性营养不良有关。然而，黄曲霉毒素在肝脏疾病的存在下会积累，并且与肝癌的关系因乙型肝炎的发生而复杂化。因此，在这些各种情况下，黄曲霉毒素是否是疾病的主要病因、是否是无辜的旁观者因疾病过程而继发积累，或者是否与其他因素共同作用尚不清楚。黄曲霉毒素还具有诱变性和致畸性。吸入黄曲霉毒素可能会引起肺腺瘤病。黄曲霉毒素通过影响抗体形成、补体、细胞介导免疫和吞噬作用来改变免疫系统。

The main target organ in mammals is the liver so aflatoxicosis is primarily a hepatic disease. Protracted exposure to aflatoxins may cause liver damage and necrosis, cholestasis, and hepatomas. Moreover, protracted exposure to aflatoxins has been associated with hepatocellular carcinoma, acute hepatitis, Reye's syndrome, bile duct cell proliferation, periportal fibrosis, hemorrhages, mucous membrane jaundice, fatty liver changes, cirrhosis in malnourished children, and kwashiorkor. However, aflatoxins accumulate in the presence of liver disease, and the association with hepatic cancer is confounded by the occurrence of hepatitis-B. Thus, it is not clear in these various instances whether aflatoxin is a primary cause of the disease, is an innocent bystander which accumulates secondary to the disease process, or is a contributing cause in conjunction with other factors. It is also mutagenic and teratogenic. Inhaled aflatoxins may produce pulmonary adenomatosis. Aflatoxins modify the immune system by affecting antibody formation, complement, cell-mediated immunity, and phagocytosis. (A704, L1956)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服、皮肤、吸入和 parenteral（被污染的药物）。 (A3101)

Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

根据剂量的不同，可能会出现一系列广泛的症状，包括呕吐、腹痛、出血和肺水肿。

A broad range of symptoms can be found depending upon dosage, including, vomiting, abdominal pain, hemorrhage, and pulmonary edema. (L1879)

来源:Toxin and Toxin Target Database (T3DB)

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

生物活性

Aflatoxin R0 是 Aflatoxin B1 的代谢物，由Rhizopus spp.产生，是一种具有诱变和致癌性的真菌毒素。