3-(2-氨基乙基)-1H-吲哚-4,5-二酮 | 108560-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 3-(2-氨基乙基)-1H-吲哚-4,5-二酮
• 中文别名: 咪唑并[1,2-a]吡嗪-3(7H)-酮,6-(4-羟基苯基)-2-[(4-羟基苯基)甲基]-8-(2-甲基丙基)-
• 英文名称: Tryptamine-4,5-dione
• 英文别名: 3-(2-aminoethyl)-1H-indole-4,5-dione
• CAS: 108560-71-0
• 化学式: C₁₀H₁₀N₂O₂
• 分子量: 190.202
• InChiKey: IEEQBAOIHWUWBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-(2-氨基乙基)-1H-吲哚-4,5-二酮 生成 5-hydroxytryptamine-4,7-dione
  参考文献：
  名称：

  WRONA, M. Z.;DRYHURST, G., J. ORG. CHEM., 52,(1987) N 13, 2817-2825

  摘要：

  DOI：
• 作为产物：
  描述：

  5-羟基色胺 在 dipotassium hydrogenphosphate 作用下， 以 水 为溶剂， 生成 3-(2-氨基乙基)-1H-吲哚-4,5-二酮
  参考文献：
  名称：

  Electrochemical Oxidation of Histamine and Serotonin at Highly Boron-Doped Diamond Electrodes

  摘要：

  使用多晶掺硼金刚石薄膜电极研究了组胺和血清素在中性水介质（pH 值为 7.2）中的电化学反应。研究中使用了循环伏安法、流体动力伏安法和带有安培检测功能的流动注射分析法（FIA）来研究氧化反应。使用抛光玻璃碳（GC）电极进行了对比实验。在金刚石电极上，组胺的循环伏安图具有高度的重现性和清晰度，峰值电位为 1.40 V vs SCE。在分析物浓度达到或超过 100 μM 时，金刚石电极获得的伏安信号-背景比比 GC 电极高出 1 个数量级。伏安测量的线性动态范围为 3-4 个数量级，检测限为 1 μM。对于 5- 羟色胺（5-HT），也获得了清晰的扫描速率依赖性伏安图。伏安图的特征表明其表面没有吸附其氧化产物。在几个小时的实验时间内，没有观察到电极堵塞或失活现象。通过使用金刚石电极的 FIA 技术，组胺的检出限为 0.5 μM（信噪比为 13.8）。用同样的方法在金刚石电极上对 5-HT 的检测限也非常低（10 nM）。金刚石电极测定 5-HT 的线性动态范围为 10 nM 至 100 μM，测定组胺的线性动态范围为 0.5 至 100 μM。不同薄膜之间的 FIA 反应具有很高的重现性，在实际检测限内的反应变异性低于 7%。

  DOI：

  10.1021/ac9908748

文献信息

• Neurotoxicity of free-radical-mediated serotonin neurotoxin in cultured embryonic chick brain neurons
  作者：Jin-Chung Chen、Richard E. Fine、Joseph Squicciarini、Ladislav Volicer

  DOI：10.1016/0014-2999(96)00059-3

  日期：1996.5

  tryptamine-4,5-dione and glutathione conjugate could not be blocked by fluoxetine (10 or 100 microM) or by a glutathione transferase inhibitor, boric acid/serine. The results indicate a different molecular mechanism among 5-HT derived neurotoxins and suggest that tryptamine-4,5-dione and/or its glutathione conjugate would cause neuronal damage, if they are formed in vivo.

  血清素（5-HT）暴露于氧衍生的自由基生成系统，黄嘌呤氧化酶-次黄嘌呤或Fenton反应导致神经毒素，色胺4,5-二酮的形成。在培养的胚胎鸡脑神经元中，色胺4,5-二酮或其碳酸乙酯衍生物的孵育导致剂量依赖性神经毒性（1-100 microM）。以2或10 microM加入巯基化合物，谷胱甘肽显着增强了10 microM tryptamine-4,5-dione诱导的毒性。相反，在培养的神经元中，10 microM的谷胱甘肽降低了10 microM 5,6-和5,7-dihydroxytryptamine引起的神经毒性作用。5-HT摄取抑制剂氟西汀可完全预防由5,6-和5,7-二羟基色胺引起的毒性。但是，由色胺4引起的毒性 氟西汀（10或100 microM）或谷胱甘肽转移酶抑制剂硼酸/丝氨酸不能阻断5-dione和谷胱甘肽共轭物。结果表明5-HT衍生的神经毒素之间的分子机制不同，并暗示如果它们在体内形成，色胺-4
• Serotonin as a physiological substrate for myeloperoxidase and its superoxide-dependent oxidation to cytotoxic tryptamine-4,5-dione
  作者：Valdecir F. Ximenes、Ghassan J. Maghzal、Rufus Turner、Yoji Kato、Christine C. Winterbourn、Anthony J. Kettle

  DOI：10.1042/bj20090776

  日期：2010.1.1

  During inflammatory events, neutrophils and platelets interact to release a variety of mediators. Neutrophils generate superoxide and hydrogen peroxide, and also discharge the haem enzyme myeloperoxidase. Among numerous other mediators, platelets liberate serotonin (5-hydroxytryptamine), which is a classical neurotransmitter and vasoactive amine that has significant effects on inflammation and immunity. In the present study, we show that serotonin is a favoured substrate for myeloperoxidase because other physiological substrates for this enzyme, including chloride, did not affect its rate of oxidation. At low micromolar concentrations, serotonin enhanced hypochlorous acid production by both purified myeloperoxidase and neutrophils. At higher concentrations, it almost completely blocked the formation of hypochlorous acid. Serotonin was oxidized to a dimer by myeloperoxidase and hydrogen peroxide. It was also converted into tryptamine-4,5-dione, especially in the presence of superoxide. This toxic quinone was produced by stimulated neutrophils in a reaction that required myeloperoxidase. In plasma, stimulated human neutrophils oxidized serotonin to its dimer using the NADPH oxidase and myeloperoxidase. We propose that myeloperoxidase will oxidize serotonin at sites of inflammation. In doing so, it will impair its physiological functions and generate a toxic metabolite that will exacerbate inflammatory tissue damage. Consequently, oxidation of serotonin by myeloperoxidase may profoundly influence inflammatory processes.

  在炎症过程中，中性粒细胞和血小板相互作用，释放出多种介质。中性粒细胞会产生超氧化物和过氧化氢，还会释放髓过氧化物酶。在众多其他介质中，血小板会释放血清素（5-羟色胺），这是一种经典的神经递质和血管活性胺，对炎症和免疫有显著影响。本研究表明，血清素是髓过氧化物酶的首选底物，因为该酶的其他生理底物（包括氯化物）不会影响其氧化速度。在低微摩尔浓度下，血清素可促进纯化的髓过氧化物酶和中性粒细胞产生次氯酸。在较高浓度下，它几乎完全阻止了次氯酸的形成。羟色胺会被髓过氧化物酶和过氧化氢氧化成二聚体。它还会转化成色胺-4,5-二酮，尤其是在有超氧化物存在的情况下。这种有毒的醌是由受刺激的中性粒细胞在需要髓过氧化物酶的反应中产生的。在血浆中，受刺激的人体中性粒细胞利用 NADPH 氧化酶和髓过氧化物酶将血清素氧化为二聚体。我们认为，髓过氧化物酶会在炎症部位氧化血清素。在此过程中，它将损害血清素的生理功能，并产生一种有毒的代谢物，从而加剧炎症组织的损伤。因此，髓过氧化物酶对血清素的氧化可能会对炎症过程产生深远影响。
• Superoxide dismutase mimics for the treatment of optic nerve and retinal damage
  申请人：Klimko G. Peter

  公开号：US20050130951A1

  公开（公告）日：2005-06-16

  Methods for preventing and treating damage to the optic nerve and/or retina by the use of SOD mimics, particularly pentaazacycle Mn (II) complex SOD mimics, are disclosed.

  通过使用 SOD 模拟物，特别是五氮杂环锰，预防和治疗视神经和/或视网膜损伤的方法 (II) 复合物 SOD 拟效物预防和治疗视神经和/或视网膜损伤的方法。
• Further insights into the reaction of melatonin with hydroxyl radical
  作者：Joseph A. Horstman、Monika Z. Wrona、Glenn Dryhurst

  DOI：10.1016/s0045-2068(02)00511-4

  日期：2002.10

  Recent interest has focused on the use of exogenous melatonin as an antioxidant, particularly to scavenge the highly cytotoxic hydroxyl radical (HO.) which may be generated in many pathological conditions. However, in vitro and in vivo studies aimed at assessing the antioxidant properties of melatonin have produced conflicting results. While it is known that HO, reacts with melatonin at a diffusion limited rate, very little is known about the products of this reaction. In this investigation it is shown that incubation of melatonin with a Fenton-type HO.-generating system at pH 7.4 forms a complex mixture of primary products. These include 2-hydroxymelatonin, which was isolated as its more stable oxindole tautomer, 4- and 6-hydroxymelatonin, N-acetyl-N-2-formyl-5-methoxykynurenine and 7,7'-bi-(5-methoxy-N-acetyltryptamine-4-one). Reaction pathways that might lead to these products are described. The differing biological effects of these products, while currently incompletely understood, might account for the controversy concerning the antioxidant properties of melatonin. (C) 2002 Published by Elsevier Science (USA).
• Influence of L-Cysteine on the Oxidation Chemistry of Serotonin
  作者：M.Z. Wrona、S. Singh、G. Dryhurst

  DOI：10.1006/bioo.1994.1035

  日期：1994.12

  L-Cysteine (CySH) intervenes in the normal electrochemically driven oxidation of 5-hydroxytryptamine (5-HT; serotonin) at physiological pH by scavenging the quinone imine proximate oxidation product of this indolic neurotransmitter to give 4-S-cysteinyl-5-hydroxy-tryptamine (4-S-CyS-5-HT). The latter cysteinyl conjugate is more easily electro-oxidized than 5-HT and, in the presence of free CySH, undergoes a complex series of reactions leading to 8-(2-aminoethyl)-1,2,3,5,6,9-hexahydro-5,9-dioxo-pyrrolo [3, 2-g] [1, 4] benzothiazine-2-carboxylic acid (20) and N-[7-[(2-amino-2-carboxyethyl) thio]-3-(2-aminoethyl)-1,4-dihydro-4-oxo-5H-indol-5-ylidene]-L-cysteine (4). CySH also reacts with another normal oxidation product of 5-HT, tryptamine-4,5-dione, to give 4 and 20. There is evidence that aberrant oxidative metabolism of 5-HT occurs in the brains of Alzheimer's Disease patients. In the event that such reactions occur in the cytoplasm of serotonergic nerve terminals or axons they would necessarily expose electrophilic intermediates and products to the intraneuronal nucleophiles CySH and GSH. The results of this study indicate that 4 and 20 might represent aberrant oxidative metabolites formed in such reactions. However, the ease of oxidation of 4-S-CyS-5-HT compared to 5-HT suggest that this conjugate is likely to be only a transient species in vivo under conditions where the neurotransmitter is oxidized. (C) 1994 Academic Press, Inc.