(2S,3R)-4-甲氧基-4-氧代-2,3-二-巯基丁酸 | 73618-85-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (2S,3R)-4-甲氧基-4-氧代-2,3-二-巯基丁酸
• 中文别名: 1H-苯并咪唑,2-(氯氟甲基)-6-甲基-
• 英文名称: (R*,S*)-Monomethyl 2,3-dimercaptobutanedioate
• 英文别名: (2S,3R)-4-methoxy-4-oxo-2,3-bis(sulfanyl)butanoic acid
• CAS: 73618-85-6
• 化学式: C₅H₈O₄S₂
• 分子量: 196.248
• InChiKey: GELAOSIUBCMYGY-GBXIJSLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  65.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  甲醇 、 succimer 以 acidic aq. solution 为溶剂， 生成 (2S,3R)-4-甲氧基-4-氧代-2,3-二-巯基丁酸
  参考文献：
  名称：

  Reversal of Arsenic-Induced Hepatic Apoptosis with Combined Administration of DMSA and Its Analogues in Guinea Pigs: Role of Glutathione and Linked Enzymes

  摘要：

  Arsenicosis, due to contaminated drinking water in the Indo-Bangladesh region, is a serious health hazard in terms of morbidity and mortality. Reactive oxygen species (ROS) generated due to arsenic toxicity have been attributed as one of the initial signals that impart cellular toxicity, which is controlled by the internal antioxidant glutathione (GSH). In the present study, we investigated (i) the role of GSH and its linked enzymes, glutathione peroxidase and glutathione reductase, in reversing chronic arsenic toxicity using a thiol chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), or one of its analogues individually or in combination; (ii) if alterations in the carbon side chain of DMSA increased efficacy; and (iii) whether the combination therapy enhance arsenic removal from hepatic tissue and prevent hepatic apoptosis. Results indicated that chronic arsenic exposure led to a ROS-mediated, mitochondrial-driven, caspase-dependent apoptosis in hepatic cells with a significant increase in glutathione disulfide (GSSG) levels and decreased glutathione reductase levels. Monotherapy with DMSA and its analogues did show minimal recovery postchelation. However, the combination of DMSA with long carbon chain analogues like monoisoamyl DMSA (MiADMSA) or monocyclohexyl DMSA (MchDMSA) showed a better efficacy in terms of reducing the arsenic burden as well as reversing altered biochemical variables indicative of oxidative stress and apoptosis. We also observed that GSH and its linked enzymes, especially glutathione reductase, play a vital role in scavenging ROS, maintaining GSH pools, and providing clinical recoveries. On the basis of the above observations, we recommend that combinational therapy of DMSA and its long carbon chain analogues MiADMSA or MchDMSA would be more effective in arsenic toxicity.

  DOI：

  10.1021/tx700315a

文献信息

• Reversal of Arsenic-Induced Hepatic Apoptosis with Combined Administration of DMSA and Its Analogues in Guinea Pigs: Role of Glutathione and Linked Enzymes
  作者：Deepshikha Mishra、Ashish Mehta、Swaran J. S. Flora

  DOI：10.1021/tx700315a

  日期：2008.2.1

  Arsenicosis, due to contaminated drinking water in the Indo-Bangladesh region, is a serious health hazard in terms of morbidity and mortality. Reactive oxygen species (ROS) generated due to arsenic toxicity have been attributed as one of the initial signals that impart cellular toxicity, which is controlled by the internal antioxidant glutathione (GSH). In the present study, we investigated (i) the role of GSH and its linked enzymes, glutathione peroxidase and glutathione reductase, in reversing chronic arsenic toxicity using a thiol chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), or one of its analogues individually or in combination; (ii) if alterations in the carbon side chain of DMSA increased efficacy; and (iii) whether the combination therapy enhance arsenic removal from hepatic tissue and prevent hepatic apoptosis. Results indicated that chronic arsenic exposure led to a ROS-mediated, mitochondrial-driven, caspase-dependent apoptosis in hepatic cells with a significant increase in glutathione disulfide (GSSG) levels and decreased glutathione reductase levels. Monotherapy with DMSA and its analogues did show minimal recovery postchelation. However, the combination of DMSA with long carbon chain analogues like monoisoamyl DMSA (MiADMSA) or monocyclohexyl DMSA (MchDMSA) showed a better efficacy in terms of reducing the arsenic burden as well as reversing altered biochemical variables indicative of oxidative stress and apoptosis. We also observed that GSH and its linked enzymes, especially glutathione reductase, play a vital role in scavenging ROS, maintaining GSH pools, and providing clinical recoveries. On the basis of the above observations, we recommend that combinational therapy of DMSA and its long carbon chain analogues MiADMSA or MchDMSA would be more effective in arsenic toxicity.