2-tert-butyl-5-glutathion-S-ylhydroquinone | 139035-70-4

• 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
• 英文名称: 2-tert-butyl-5-glutathion-S-ylhydroquinone
• 英文别名: 5-(S-Glutathionyl)-2-tert-butylhydroquinone；(2S)-2-amino-5-[[(2R)-3-(4-tert-butyl-2,5-dihydroxyphenyl)sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 139035-70-4
• 化学式: C₂₀H₂₉N₃O₈S
• 分子量: 471.532
• InChiKey: ZOFLHFUJRPXAAO-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  225
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  谷胱甘肽 、 叔丁基对苯醌 在 Tween 20 作用下， 反应 0.08h， 生成 2-tert-butyl-5-glutathion-S-ylhydroquinone
  参考文献：
  名称：

  Activation of the NRF2 Signaling Pathway by Copper-Mediated Redox Cycling of Para- and Ortho-Hydroquinones

  摘要：

  Transcription factor NF-E2 p45-related factor 2 (Nrf2) mediates adaptation to oxidants and electrophiles through up-regulating genes that contain antioxidant response elements (AREs) in their promoters. Using the stably transfected human AREc32 reporter cell line, we found that copper and other transition metals enhanced induction of ARE-driven luciferase by 2-tert-butyl-1,4-hydroquinone (tBHQ) as a result of increased oxidation to 2-tert-butyl-1,4-benzoquinone (tBQ). Following exposure to tBHQ for 30 min, ARE-luciferase activity measured after 24 hr was dependent on the presence of Cu2+. In contrast, tBQ-induced activity was Cu2+-independent. The metal-catalyzed oxidation of tBHQ to tBQ occured rapidly and stoichiometrically. Compounds that share para- or ortho-hydroquinone structures, such as catechol estrogens, dopamine, and L-DOPA, also induced ARE-driven luciferase in a Cu2+-dependent manner. Thus, the oxidation of para- and orthohydroquinones to quinones represents the rate-limiting step in the activation of Nrf2.

  DOI：

  10.1016/j.chembiol.2009.12.013

文献信息

• Metabolism of <i>tert</i>-Butylhydroquinone to <i>S</i>-Substituted Conjugates in the Male Fischer 344 Rat
  作者：Melanie M. C. G. Peters、Serrine S. Lau、Deanne Dulik、Darlene Murphy、Ben van Ommen、Peter J. van Bladeren、Terrence J. Monks

  DOI：10.1021/tx950122i

  日期：1996.1.1

  tert-Butyl-4-hydroxyanisole (BHA) and its demethylated analog, tert-butyl-hydroquinone (TBHQ), are antioxidants used in food. Both BHA and TBHQ have been shown to promote kidney and bladder carcinogenesis in the rat. We have previously demonstrated that glutathione (GSH) conjugates of a variety of hydroquinones are nephrotoxic and proposed that GSH conjugation serves to target these compounds to the kidney. In the present study, we examined the metabolism of TBHQ, focusing on the formation of potentially nephrotoxic sulfur-containing metabolites. 2-tert-Butyl-5-glutathion-S-ylhydroquinone, 2-tert-butyl-6-glutathion-S-ylhydroquinone, and 2-tert-butyl-3,6-bisglutathion-S-ylhydroquinone were identified as biliary metabolites of TBHQ (1.0 mmol/kg, ip) in male F344 rats, accounting for 2.2% of the dose. Liquid chromatography/mass spectroscopic analysis of urine also revealed the presence of additional sulfur-containing metabolites, tentatively identified as 2,5-dihydroxy-3-tert-butylthiophenol, 2,5-dihydroxy-4-tert-butylthiophenol, and their S-methyl derivatives. No mercapturic acids of TBHQ were found in the urine. The major biliary and urinary metabolites were TBHQ-glucuronide and TBHQ-sulfate, with a trace of TBHQ excreted unchanged. The results indicate that TBHQ undergoes oxidation and GSH conjugation in vivo in the male F344 rat. These conjugates are excreted into bile and undergo further metabolism prior to excretion in urine. Formation of the S-containing metabolites of TBHQ may occur in amounts sufficient to play a role in the toxicity of TBHQ to kidney and bladder.
• Activation of the NRF2 Signaling Pathway by Copper-Mediated Redox Cycling of Para- and Ortho-Hydroquinones
  作者：Xiu Jun Wang、John D. Hayes、Larry G. Higgins、C. Roland Wolf、Albena T. Dinkova-Kostova

  DOI：10.1016/j.chembiol.2009.12.013

  日期：2010.1

  Transcription factor NF-E2 p45-related factor 2 (Nrf2) mediates adaptation to oxidants and electrophiles through up-regulating genes that contain antioxidant response elements (AREs) in their promoters. Using the stably transfected human AREc32 reporter cell line, we found that copper and other transition metals enhanced induction of ARE-driven luciferase by 2-tert-butyl-1,4-hydroquinone (tBHQ) as a result of increased oxidation to 2-tert-butyl-1,4-benzoquinone (tBQ). Following exposure to tBHQ for 30 min, ARE-luciferase activity measured after 24 hr was dependent on the presence of Cu2+. In contrast, tBQ-induced activity was Cu2+-independent. The metal-catalyzed oxidation of tBHQ to tBQ occured rapidly and stoichiometrically. Compounds that share para- or ortho-hydroquinone structures, such as catechol estrogens, dopamine, and L-DOPA, also induced ARE-driven luciferase in a Cu2+-dependent manner. Thus, the oxidation of para- and orthohydroquinones to quinones represents the rate-limiting step in the activation of Nrf2.