S-allyl 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-allyl glutathione
• 英文别名: S-allyl-glutathione；S-allylglutathione；γ-Glu-Cys(S-allyl)-Gly；γ-Glu-Cys(allyl)-Gly；GSA；SAG；(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-prop-2-enylsulfanylpropan-2-yl]amino]-5-oxopentanoic acid
• 化学式: C₁₃H₂₁N₃O₆S
• 分子量: 347.392
• InChiKey: HYWLPDOKCGRIQZ-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  23
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  184
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  谷胱甘肽 、 3-溴丙烯 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 以58%的产率得到S-allyl glutathione
  参考文献：
  名称：

  Metabolism of the Chemoprotective Agent Diallyl Sulfide to Glutathione Conjugates in Rats

  摘要：

  The chemoprotective effects of diallyl sulfide (DAS), a flavor component of garlic, have been attributed to its inhibitory effects on CYP2E1-mediated bioactivation of certain carcinogenic chemicals. In addition to being a competitive inhibitor of CYP2E1 in vitro, DAS is known to cause irreversible inhibition of CYP2E1 in rats in vivo. The latter property is believed to be mediated by the DAS metabolite diallyl sulfone (DASO(2)), which is thought to be a mechanism-based inhibitor of CYP2E1, although the underlying mechanism remains unknown. In order to investigate the nature of the reactive intermediate(s) responsible for the inactivation of CY2BE1 by DAS and its immediate metabolites, the present studies were carried out to detect and identify potential glutathione (GSH) conjugates of DAS and its metabolites diallyl sulfoxide (DASO) and DASO(2). By means of ionspray LC-MS/MS, ten GSH conjugates were identified in bile collected from rats dosed with DAS, namely: S-[3-(S'-allyl-S'-oxomercapto)-2-hydroxypropyl]glutathione (M1, M2; diastereomers), S-[3-(S'-allyl-S'-dioxomercapto)-2-hydroxypropyl]-glutathione (M5), S-[2-(S'-allyl-S'-dioxomercapto)-1-(hydroxymethyl)ethyl]glutathione (M3, M4; diastereomers), S-[3-(S'-allylmercapto)-2-hydroxypropyl]glutathione(M6), S-(3-hydroxypropyl)-glutathione (M7), S-(2-carboxyethyl)glutathione (M8), allyl glutathionyl disulfide (M9), and S-allylglutathione (M10). With the exception of M6, all of the above GSH conjugates were detected in the bile of rats treated with DASO, while only M3, M4, M5, M8, and M10 were found in the bile of rats treated with DASO(2). Experiments conducted in vitro showed that GSH reacted spontaneously with DASO to form conjugates M9 and M10, and with DASO(2) to form M10. In the presence of NADPH and GSH, incubation of DAS with cDNA-expressed rat CYP2E1 resulted in the formation of metabolites M6, M9, and M10, while incubation with DASO led to the formation of M3, M4, M5, M9, and M10. When DASO(2) acted as substrate, CY2BE1 generated only conjugates M3, M4, M5, and M10. These results indicate that while DAS and DASO undergo extensive oxidation in vice at the sulfur atom, the allylic carbon, and the terminal double bonds, CY2BE1 preferentially catalyzes oxidation of the sulfur atom to form the sulfoxide and the sulfone (DASO and DASO(2)). However, it appears that the end product of this sequence, namely, DASO(2), undergoes further CYP2E1-mediated activation of the olefinic pi-bond, a reaction which transforms many terminal olefins to potent mechanism-based P450 inhibitors. We hypothesize, therefore, that it is this final metabolic event with DASO(2) which leads to autocatalytic destruction of CYP2E1 and which is mainly responsible for the chemoprotective effects of DAS in vivo.

  DOI：

  10.1021/tx9601768

文献信息

• REMEDIES FOR BRAIN DISEASES
  申请人：WAKUNAGA PHARMACEUTICAL CO., LTD.

  公开号：EP0885608A1

  公开（公告）日：1998-12-23

  The present invention discloses the use, in the manufacture of a preventive and therapeutic drug of a brain disease, of a compound represented by formula (1):         CH2=CH-CH2-S(O)n-R     (1) [wherein R represents a hydrogen atom, an alkyl group, an alkenyl group, a substituted alkyl group, a substituted alkenyl group, an alkylthio group, an alkenylthio group, a phenyl group, a substituted phenyl group, a heterocyclic group, or a group derived from an amino acid or an oligopeptide by deletion of one hydrogen atom, and which group may have a protective group; and n is 0, 1, or 2], a glycoside thereof, or a salt of the compound or the glycoside. The drug of the present invention for ameliorating brain diseases, inhibiting reduction of brain neurons and promoting branching of neurites, is useful for the prevention and treatment of brain diseases such as dementia in association with degeneration and sloughing of brain neurons.

  本发明公开了式 (1) 所代表的化合物在制造脑疾病预防和治疗药物中的用途： CH2=CH- -S(O)n-R (1) [其中 R 代表氢原子、烷基、烯基、取代的烷基、取代的烯基、烷硫基、烯硫基、苯基、取代的苯基、杂环基、或由氨基酸或低聚肽去掉一个氢原子衍生的基团，该基团可带有保护基；且 n 为 0、1 或 2]、其糖苷或该化合物或该糖苷的盐。 本发明用于改善脑部疾病、抑制脑神经元减少和促进神经元分支的药物可用于预防和治疗与脑神经元变性和脱落有关的痴呆等脑部疾病。
• Diallyl Trisulfide Is a Fast H₂S Donor, but Diallyl Disulfide Is a Slow One: The Reaction Pathways and Intermediates of Glutathione with Polysulfides
  作者：Dong Liang、Haixia Wu、Ming Wah Wong、Dejian Huang

  DOI：10.1021/acs.orglett.5b01962

  日期：2015.9.4

  Diallyl trisulfide (DATS) reacts rapidly with glutathione (GSH) to release H2S through thiol-disulfide exchange followed by allyl perthiol reduction by GSH. Yet diallyl disulfide (DADS) only releases a minute amount of H2S via a sluggish reaction with GSH through an alpha-carbon nucleophilic substitution pathway. The results clarify the misunderstanding of DADS as a rapid H2S donor, which is attributed to its DATS impurity.
• US3950387A
  申请人：——

  公开号：US3950387A

  公开（公告）日：1976-04-13
• US3984569A
  申请人：——

  公开号：US3984569A

  公开（公告）日：1976-10-05
• US6239111B1
  申请人：——

  公开号：US6239111B1

  公开（公告）日：2001-05-29