aflatoxin B1 8,9-epoxide

• 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: aflatoxin B1 8,9-epoxide
• 英文别名: 12-Methoxy-5,7,9,20-tetraoxahexacyclo[11.7.0.02,10.03,8.04,6.014,18]icosa-1,10,12,14(18)-tetraene-17,19-dione
• 化学式: C₁₇H₁₂O₇
• 分子量: 328.278
• InChiKey: KHBXRZGALJGBPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  83.6
• 氢给体数：
  0
• 氢受体数：
  7

ADMET

代谢

已知黄曲霉毒素B1外环氧化物在人体内的代谢物包括(2S)-2-氨基-5-[[(2R)-1-(羧甲基氨基)-3-[(4-羟基-11-甲氧基-16,18-二氧代-6,8,19-三氧杂五环[10.7.0.02,9.03,7.013,17]十九烷-1,9,11,13(17)-四烯-5-基)硫anyl]-1-氧代丙烷-2-基]氨基]-5-氧代戊酸。

Aflatoxin B1 exo 8,9-epoxide has known human metabolites that include (2S)-2-Amino-5-[[(2R)-1-(carboxymethylamino)-3-[(4-hydroxy-11-methoxy-16,18-dioxo-6,8,19-trioxapentacyclo[10.7.0.02,9.03,7.013,17]nonadeca-1,9,11,13(17)-tetraen-5-yl)sulfanyl]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  aflatoxin B1 在 二甲基二环氧乙烷 作用下， 以 丙酮 为溶剂， 反应 0.33h， 生成 aflatoxin B1 8,9-epoxide
  参考文献：
  名称：

  Effect of dietary restriction on glutathione S-transferase activity specific toward aflatoxin B1-8,9-epoxide

  摘要：

  Dietary restriction (DR) reduced the metabolic activation of aflatoxin B1 (AFB(1)) in rats, This reduction may be attributed to the decrease of cytochrome P-450-mediated AFB(1) epoxidation and/or increase in the detoxification of AFB(1) catalyzed by hepatic glutathione S-transferase (GST) and other phase II detoxification enzymes. In this study the effect of DR on male rat liver cytosolic GST activity toward AFB(1)-8,9-epoxide was studied. The chemically-synthesized AFB(1)-8,9-epoxide was used as the substrate in this assay, and the formation of AFB(1)-GSH conjugate was analyzed by HPLC. Male Fischer 344 rats fed DR diets (60% of the food consumption of ad libitum (AL)-fed rats) showed a 2.4-fold increase in GST activity when AFB(1)-epoxide was used as the substrate. The results from the enzyme kinetic study showed that DR increased V-max of the liver cytosolic GST but not the K-m. Acute DR has little or no impact on GST activity when 1-chloro-2,4-dinitrobenzene and 2,4-dichloronitrobenzene were used as substrates. The mouse liver GST activity toward AFB(1)-epoxide was 3-fold greater than that of phenobarbital-induced rats, 4.5-fold greater than DR rats, and 14.7-fold greater than the GST activity of AL rats, This direct assay of liver GST activity using AFB(1)-epoxide as the substrate is useful for studying AFB(1)-induced biomarkers, such as AFB(1)-GSH conjugation and AFB(1)-DNA adducts.

  DOI：

  10.1016/0378-4274(95)03263-k

文献信息

• OXIDIZED cis-TERPENONE AND ITS USE AS A CHEMOPROTECTIVE AND ANTI-MALARIAL AGENT
  申请人：Zhou Qibing

  公开号：US20090149551A1

  公开（公告）日：2009-06-11

  4 b ,5,6,7,8,8 a -cis-hexahydro-2-hydroxy-4 b ,8,8 a -trimethylphenanthren-9,10-dione (OHCT) is a fully oxidized compound based on the 2-hydroxy-cis-terpenone (HCT). Because OHCT is fully oxidized, it is more stable and less likely to damage cells or cell constituents such as DNA. OHCT has antimalarial activity, noncompetitive inhibitory activity against carcinogenic conversion of aflotoxin B1 (AFB1) to exo-AFB1-epoxide thus inihibiting AFB1 induced cellular toxicity, and inhibitory activity against TCDD induced cellular toxicity.