S-(N-Phenylethylthiocarbamoyl)glutathione

• 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: S-(N-Phenylethylthiocarbamoyl)glutathione
• 英文别名: L-Gamma-Glutamyl-S-[(2-Phenylethyl)carbamothioyl]-L-Cysteinylglycine；(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-(2-phenylethylcarbamothioylsulfanyl)propan-2-yl]amino]-5-oxopentanoic acid
• 化学式: C₁₉H₂₆N₄O₆S₂
• 分子量: 470.571
• InChiKey: WSGBVCNCZSZCGE-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  31
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  228
• 氢给体数：
  6
• 氢受体数：
  9

ADMET

代谢

(2S)-2-氨基-5-[[(2R)-1-(羧甲基氨基)-1-氧代-3-(2-苯乙基碳氨基硫基)丙烷-2-基]氨基]-5-氧代戊酸是苯乙基异硫氰酸酯的人类已知代谢物。

(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-(2-phenylethylcarbamothioylsulfanyl)propan-2-yl]amino]-5-oxopentanoic acid is a known human metabolite of phenethyl isothiocyanate.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  S-(N-Phenylethylthiocarbamoyl)glutathione 以 水 、 二甲基亚砜 为溶剂， 生成 谷胱甘肽 、 2-苯基乙基异硫代氰酸酯
  参考文献：
  名称：

  异硫氰酸酯结合物的分解速率决定了它们作为细胞色素p450酶抑制剂的活性。

  摘要：

  异硫氰酸酯（硫醇-ITC）的硫醇共轭物是哺乳动物巯基酸途径中形成的ITC的代谢产物。它们在小鼠肺肿瘤生物测定和其他模型中是有效的化学预防剂。硫醇-ITC是P450的抑制剂，但尚未确定P450的抑制是由于缀合物本身还是由于去共轭反应释放的母体ITC所致。在研究硫醇-ITC的化学预防作用机理时，异硫氰酸苄酯（BITC），苯乙基异硫氰酸酯（PEITC），6-苯基己基异硫氰酸酯（半胱氨酸，半胱氨酸和N-乙酰基-L-半胱氨酸（NAC）缀合物的去偶联率） PHITC）和萝卜硫烷（SFN），表示为一级速率常数k（1）和分解半衰期Dt（1/2），是在pH 7.4和37度的水溶液中测量的。Cys缀合物的Dt（1/2）s比各个GSH缀合物的Dt（1/2）s短几倍，而NAC缀合物的Dt（1/2）s最长。硫醇缀合物的裂解是pH依赖性的，在酸性条件下比在pH 7.4下慢得多。随后对P450 2B1使用PROD（戊氧

  DOI：

  10.1021/tx010029w
• 作为产物：
  描述：

  谷胱甘肽 、 2-苯基乙基异硫代氰酸酯 以 phosphate buffer 为溶剂， 生成 S-(N-Phenylethylthiocarbamoyl)glutathione
  参考文献：
  名称：

  Inhibition of human leukaemia 60 cell growth by mercapturic acid metabolites of phenylethyl isothiocyanate

  摘要：

  Mercapturic acid pathway metabolites of phenylethyl isothiocyanate inhibited the growth of human leukaemia 60 (HL60) cells in vitro. The adduct with L-cysteine, S-(N-phenylethylthiocarbamoyl)cysteine, was the most potent with strong antileukaemic activity: the median growth inhibitory concentration (GC(50)) value was 336 +/- 1 nM (N = 18) compared with GC(50) values of the precursor formed from dietary glucosinolates, phenylethyl isothiocyanate, 1.49 +/- 0.01 mu M (N = 8), and the initial mercapturic acid pathway metabolite S-(N-phenylethylthiocarbamoyl)glutathion 5.46 +/- 0.36 mu M (N = 18). S-(N-Benzylthiocarbamoyl)cysteine and S-(N-phenylpropylthiocarbamoyl)cysteine also had antiproliferative activity but S-(N-phenylethylthiocarbamoyl)cysteine was the most potent compound studied. The latter induced DNA fragmentation in HL60 cells but DNA laddering characteristic of apoptosis was not observed. It had low toxicity to corresponding differentiated cells, neutrophils, in culture, and therefore the cytotoxicity had selectivity for leukaemia cells. The antiproliferative activity of S-(N-phenylethylthiocarbamoyl)cysteine was lost during preincubation with culture medium, attributed to S-thiocarbamoyl transfer to serum proteins, which may decrease its effectiveness in vivo. The antiproliferative activity of S-(N-phenylalkylthiocarbamoyl)cysteine derivatives, by inhibiting tumour growth in pre-clinical development, may contribute to the association of decreased cancer incidence with dietary glucosinolate consumption. (C) 1996 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/0278-6915(96)00124-x

文献信息

• Decomposition Rates of Isothiocyanate Conjugates Determine Their Activity as Inhibitors of Cytochrome P450 Enzymes
  作者：C. Clifford Conaway、Jacek Krzeminski、Shantu Amin、Fung-Lung Chung

  DOI：10.1021/tx010029w

  日期：2001.9.1

  isothiocyanates (thiol-ITCs) are metabolites of ITCs formed in the mercapturic acid pathway in mammals. They are effective chemopreventive agents in mouse lung tumor bioassays and in other models. Thiol-ITCs are inhibitors of P450s, but it has not been determined if P450 inhibition is due to conjugates themselves or to parent ITCs released by deconjugation reactions. In studies of mechanism of chemopreventive action

  异硫氰酸酯（硫醇-ITC）的硫醇共轭物是哺乳动物巯基酸途径中形成的ITC的代谢产物。它们在小鼠肺肿瘤生物测定和其他模型中是有效的化学预防剂。硫醇-ITC是P450的抑制剂，但尚未确定P450的抑制是由于缀合物本身还是由于去共轭反应释放的母体ITC所致。在研究硫醇-ITC的化学预防作用机理时，异硫氰酸苄酯（BITC），苯乙基异硫氰酸酯（PEITC），6-苯基己基异硫氰酸酯（半胱氨酸，半胱氨酸和N-乙酰基-L-半胱氨酸（NAC）缀合物的去偶联率） PHITC）和萝卜硫烷（SFN），表示为一级速率常数k（1）和分解半衰期Dt（1/2），是在pH 7.4和37度的水溶液中测量的。Cys缀合物的Dt（1/2）s比各个GSH缀合物的Dt（1/2）s短几倍，而NAC缀合物的Dt（1/2）s最长。硫醇缀合物的裂解是pH依赖性的，在酸性条件下比在pH 7.4下慢得多。随后对P450 2B1使用PROD（戊氧
• Inhibition of human leukaemia 60 cell growth by mercapturic acid metabolites of phenylethyl isothiocyanate
  作者：A. Adesida、L.G. Edwards、P.J. Thornalley

  DOI：10.1016/0278-6915(96)00124-x

  日期：1996.4

  Mercapturic acid pathway metabolites of phenylethyl isothiocyanate inhibited the growth of human leukaemia 60 (HL60) cells in vitro. The adduct with L-cysteine, S-(N-phenylethylthiocarbamoyl)cysteine, was the most potent with strong antileukaemic activity: the median growth inhibitory concentration (GC(50)) value was 336 +/- 1 nM (N = 18) compared with GC(50) values of the precursor formed from dietary glucosinolates, phenylethyl isothiocyanate, 1.49 +/- 0.01 mu M (N = 8), and the initial mercapturic acid pathway metabolite S-(N-phenylethylthiocarbamoyl)glutathion 5.46 +/- 0.36 mu M (N = 18). S-(N-Benzylthiocarbamoyl)cysteine and S-(N-phenylpropylthiocarbamoyl)cysteine also had antiproliferative activity but S-(N-phenylethylthiocarbamoyl)cysteine was the most potent compound studied. The latter induced DNA fragmentation in HL60 cells but DNA laddering characteristic of apoptosis was not observed. It had low toxicity to corresponding differentiated cells, neutrophils, in culture, and therefore the cytotoxicity had selectivity for leukaemia cells. The antiproliferative activity of S-(N-phenylethylthiocarbamoyl)cysteine was lost during preincubation with culture medium, attributed to S-thiocarbamoyl transfer to serum proteins, which may decrease its effectiveness in vivo. The antiproliferative activity of S-(N-phenylalkylthiocarbamoyl)cysteine derivatives, by inhibiting tumour growth in pre-clinical development, may contribute to the association of decreased cancer incidence with dietary glucosinolate consumption. (C) 1996 Elsevier Science Ltd. All rights reserved.