acide dithiole-1,3 thioxo-2 carboxylique-4 | 1004-08-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: acide dithiole-1,3 thioxo-2 carboxylique-4
• 英文别名: 1.3-Dithiol-2-thion-4-carbonsaeure；2-thioxo-1,3-dithiol-4-carboxylic acid；1,3-dithiole-2-thioxo-4-carboxylic acid；ACS 5；2-thioxo-[1,3]dithiole-4-carboxylic acid；2-Thioxo-1,3-dithiole-4-carboxylic acid；2-sulfanylidene-1,3-dithiole-4-carboxylic acid
• CAS: 1004-08-6
• 化学式: C₄H₂O₂S₃
• 分子量: 178.257
• InChiKey: MDHFTORBCQQLPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  acide dithiole-1,3 thioxo-2 carboxylique-4 、 伏立诺他 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以31%的产率得到N¹-phenyl-N⁸-(2-thioxo-1,3-dithiol-4-carbonyloxy)octanediamide
  参考文献：
  名称：

  New aryldithiolethione derivatives as potent histone deacetylase inhibitors

  摘要：

  A series of dithiolethione derivatives was synthesized and the in vitro HDAC inhibitory activity was tested. The most active compounds, 1 and 2, exhibited an IC50 in nM range with a strong hyperacetylation of histone H4 in A549 cells. The HDAC inhibitory activity comparable to that of SAHA and the inhibition of A549 cell proliferation suggest that these compounds are worthy of further studies as potential anticancer agents. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.011
• 作为产物：
  描述：

  1,3-Dithiol-2-thion-4,5-dicarbonsaeure 反应 0.25h， 以84%的产率得到acide dithiole-1,3 thioxo-2 carboxylique-4
  参考文献：
  名称：

  一元和二元羧酸双稠合四硫富瓦烯的合成

  摘要：

  具有单和二羧酸，2- {5-（1,3-二硫醇-2-亚烷基）- [1,3]二硫代[4,5- d ] [1,3]二硫醇-2-的双融合四硫富瓦烯亚基} -1,3-二硫代-4-羧酸（1）和2- {5-（1,3-二硫代-2-亚烷基）-[1,3]二硫代[4,5- d ] [1，合成了3]二硫醇-2-亚烷基} -1，3-二硫醇-4，5-二羧酸（2）。从其1和2的电子吸收光谱和使用密度泛函计算来检查其电子结构。

  DOI：

  10.1016/j.tetlet.2012.04.064

文献信息

• Design, Synthesis and Biological Evaluations of Novel Conjugates of Danshensu, Tetramethylpyrazine and Hydrogen Sulfide Donors as Cardioprotective Agents
  作者：Chang-Jiang Xu、Hui-Xing Deng、Hai-Yun Chen、Qing-Bin Cui、Lu-Chen Shan、Pei Yu、Ye-Wei Sun、Yu-Qiang Wang

  DOI：10.14233/ajchem.2016.20101

  日期：——

  A series of molecular hybrids of Danshensu-tetramethylpyrazine-hydrogen sulfide donors have been synthesized and evaluated in vitro as potent antimyocardial ischemia agents. The pharmacological data demonstrated that compound DTA-2 exhibited the most potent protective activities against tert-butyl hydroperoxide (t-BHP) induced injury in H9c2 cells. Further study showed that DTA-2 exhibited better ROS-scavenging activity and mitochondria protective effect than its parental drug DTM, ACS48 and mixtures of these two. These results indicated that DTA-2 may work through a unique mechanism and may serve as a drug candidate for anti-myocardial ischemia therapy that require further study.

  一系列丹参酚-四甲基吡嗪-硫化氢供体的分子杂化物被合成并在体外评估为有效的抗心肌缺血药物。药理数据表明，化合物DTA-2对叔丁基过氧化氢（t-BHP）诱导的H9c2细胞损伤展现出最强的保护活性。进一步研究表明，DTA-2的清除活性氧（ROS）能力和线粒体保护效果优于其母药DTM、ACS48及这两者的混合物。这些结果表明，DTA-2可能通过独特机制发挥作用，并可能作为抗心肌缺血治疗的药物候选者，需进一步研究。
• Dartigues; Cambar; Trebaul, European Journal of Medicinal Chemistry, 1980, vol. 15, # 5, p. 405 - 412
  作者：Dartigues、Cambar、Trebaul、et al.

  DOI：——

  日期：——
• [EN] NEW ANTICANCER COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS ANTICANCERS
  申请人：SULFIDRIS S R L

  公开号：WO2009065926A3

  公开（公告）日：2009-07-30
• H₂S-Donating Doxorubicins May Overcome Cardiotoxicity and Multidrug Resistance
  作者：Konstantin Chegaev、Barbara Rolando、Daniela Cortese、Elena Gazzano、Ilaria Buondonno、Loretta Lazzarato、Marilù Fanelli、Claudia M. Hattinger、Massimo Serra、Chiara Riganti、Roberta Fruttero、Dario Ghigo、Alberto Gasco

  DOI：10.1021/acs.jmedchem.6b00184

  日期：2016.5.26

  Doxorubicin (DOXO) is one of the most effective antineoplastic agents in clinical practice. Its use is limited by acute and chronic side effects, in particular by its cardiotoxicity and by the rapid development of resistance to it. As part of a program aimed at developing new DOXO derivatives endowed with reduced cardiotoxicity, and active against DOXO-resistant tumor cells, a series of H2S-releasing DOXOs (H2S-DOXOs) were obtained by combining DOXO with appropriate H2S donor substructures. The resulting compounds were studied on H9c2 cardiomyocytes and in DOXO-sensitive U-2OS osteosarcoma cells, as well as in related cell variants with increasing degrees of DOXO-resistance. Differently from DOXO, most of the products were not toxic at 5 mu M concentration on H9c2 cells. A few of them triggered high activity on the cancer cells. H2S-DOXOs 10 and 11 emerged as the most interesting members of the series. The capacity of 10 to impair Pgp transporter is also discussed.
• Effects of Hydrogen Sulfide-releasing l-DOPA Derivatives on Glial Activation
  作者：Moonhee Lee、Valerio Tazzari、Daniela Giustarini、Ranieri Rossi、Anna Sparatore、Piero Del Soldato、Edith McGeer、Patrick L. McGeer

  DOI：10.1074/jbc.m110.115261

  日期：2010.6

  The main lesion in Parkinson disease (PD) is loss of substantia nigra dopaminergic neurons. Levodopa (L-DOPA) is the most widely used therapy, but it does not arrest disease progression. Some possible contributing factors to the continuing neuronal loss are oxidative stress, including oxidation of L-DOPA, and neurotoxins generated by locally activated microglia and astrocytes. A possible method of reducing these factors is to produce L-DOPA hybrid compounds that have antioxidant and anti-inflammatory properties. Here we demonstrate the properties of four such L-DOPA hybrids based on coupling L-DOPA to four different hydrogen sulfide-donating compounds. The donors themselves were shown to be capable of conversion by isolated mitochondria to H2S or equivalent SH- ions. This capability was confirmed by in vivo results, showing a large increase in intracerebral dopamine and glutathione after iv administration in rats. When human microglia, astrocytes, and SH-SY5Y neuroblastoma cells were treated with these donating agents, they all accumulated H2S intracellularly as did their derivatives coupled to L-DOPA. The donating agents and the L-DOPA hybrids reduced the release of tumor necrosis factor-alpha, interleukin-6, and nitric oxide from stimulated microglia, astrocytes as well as the THP-1 and U373 cell lines. They also demonstrated a neuroprotective effect by reducing the toxicity of supernatants from these stimulated cells to SH-SY5Y cells. L-DOPA itself was without effect in any of these assays. The H2S-releasing L-DOPA hybrid molecules also inhibited MAO B activity. They may be useful for the treatment of PD because of their significant anti-inflammatory, antioxidant, and neuroprotective properties.