N-(对香豆酰)血清素 | 68573-24-0

• 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: N-(对香豆酰)血清素
• 中文别名: N-(P-香豆酰)-羟色胺
• 英文名称: N-(p-coumaroyl)serotonin
• 英文别名: N-p-coumaroyl serotonin；N-p-coumaroylserotonin；4-coumaroylserotonin；N-coumaroylserotonin；N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-(4-hydroxyphenyl)-2-propenamide；p-coumaroylserotonin；N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-(4-hydroxyphenyl)prop-2-enamide
• CAS: 68573-24-0
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: WLZPAFGVOWCVMG-UHFFFAOYSA-N

物化性质

• 熔点：
  192-194?C
• 沸点：
  694.2±55.0 °C(Predicted)
• 密度：
  1.346±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  85.4
• 氢给体数：
  4
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  储存条件：室温、避光、干燥、密封。

制备方法与用途

生物活性方面，N-(p-对香豆酰基)色胺是一种从红花种子中分离出的多酚化合物，具有抗氧化、抗动脉粥样硬化以及抗炎特性。该物质能够降低肌浆网中由血小板衍生生长因子（PDGF）诱导的中膜平滑肌细胞 PDGFR 酪氨酸磷酸化和 Ca2+ 释放的作用。N-(p-对香豆酰基)色胺还能改善动脉粥样硬化并减少主动脉壁膨大，常被用于相关研究领域。

反应信息

• 作为产物：
  描述：

  5-羟基色胺 、 对羟基肉桂酸 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 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(对香豆酰)血清素
  参考文献：
  名称：

  Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

  摘要：

  We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.

  DOI：

  10.1074/jbc.m111.307199

文献信息

• Serotonin derivatives as inhibitors of -secretase (BACE 1)
  作者：Takahashi、Miyazawa, Mitsuo

  DOI：10.1691/ph.2011.0789

  日期：——

  All serotonin derivatives described here (1–9) inhibited BACE 1 in a dose dependent manner. The 50% Inhibition Concentration (IC50 ) of N -cinnamoyl serotonin (1) was 86.7 ± 4.0 M. The peptide conjugation of serotonin derivatives influenced the BACE 1 inhibitory activity. Among serotonin derivatives (1–8), introduction of substituents, such as hydroxyl and methoxy groups at the 4 -position decreased the inhibitory activity (N - p -coumaroyl serotonin (2), N - p -methoxy cinnamoyl serotonin (3)). With a hydroxylgroup at the 4 -position, and the meta -hydroxy function being substituted by a hydroxyl group or methoxy group ( N caffeoyl serotonin (4), N -feruloyl serotonin (5)), inhibitory activity was weakened, (IC50 > 400 M). BACE 1 inhibitory activity was effected by the substituents of the cinnamic acid moiety. This is the first report on Structure-Activity-Relationships (SAR) for the BACE 1-inhibiting activity of serotonin derivatives. These serotonin derivatives, which have anti-oxidative effects as well are expected to be useful in the study of the mechanisms of Alzheimer's disease.

  这里描述的所有血清素衍生物 (1-9) 均以剂量依赖性方式抑制 BACE 1。 N-肉桂酰血清素 (1) 的 50% 抑制浓度 (IC50) 为 86.7 ± 4.0 M。血清素衍生物的肽缀合影响 BACE 1 抑制活性。在血清素衍生物 (1–8) 中，4 位羟基和甲氧基等取代基的引入降低了抑制活性（N - 对香豆酰血清素 (2)、N - 对甲氧基肉桂酰血清素 (3)） 。 4位有羟基，间位羟基被羟基或甲氧基取代（N咖啡酰血清素（4）、N-阿魏酰血清素（5）），抑制活性减弱，（IC50>400）米）。 BACE 1 抑制活性受肉桂酸部分的取代基影响。这是第一份关于血清素衍生物 BACE 1 抑制活性的结构-活性-关系 (SAR) 的报告。这些血清素衍生物也具有抗氧化作用，预计可用于阿尔茨海默病机制的研究。
• Synthesis and structure–activity relationships of phenylpropanoid amides of serotonin on tyrosinase inhibition
  作者：Toshiyuki Takahashi、Mitsuo Miyazawa

  DOI：10.1016/j.bmcl.2011.02.028

  日期：2011.4

  In this manuscript, we synthesized a series of phenylpropanoid amide of serotonin 1-9, analyzed their structural importance for two biologic activities (antioxidant activity and tyrosinase inhibitory activity). While the serotonin moiety and the amide linkage of serotonin derivatives affect antioxidant activity strongly, the serotonin moiety, the amide linkage and the cinnamic acid moiety affect tyrosinase inhibitory activity. Among tested compounds, compound 4 which contains cathechol moiety exhibited the most antioxidant activity (EC50 = 19.4 +/- 2.0 mu M), and compound 6 exhibited significant tyrosinase inhibitory activity (IC50 = 5.4 +/- 3.6 mu M). Our data suggests that a useful clue for the design and development of new tyrosinase inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and structure–activity relationships of serotonin derivatives effect on α-glucosidase inhibition
  作者：Toshiyuki Takahashi、Mitsuo Miyazawa

  DOI：10.1007/s00044-011-9699-9

  日期：2012.8

  The alpha-glucosidase inhibitory activities of serotonin derivatives were evaluated. Two serotonin derivatives, N-p-coumaroyl serotonin (2) and N-caffeoyl serotonin (4) exhibited most potent inhibition on alpha-glucosidase, whereas, cinnamic acid derivatives were less efficient. Furthermore, we analyzed their structural importance for alpha-glucosidase inhibition. The linkage of cinnamic acid moiety and serotonin moiety and the olefin in cinnamic acid moiety of serotonin derivatives were crucial for alpha-glucosidase inhibition. This is the first report on structure-activity relationships (SAR) for the alpha-glucosidase inhibitory activity of serotonin derivatives.
• Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy
  作者：Chinmay Pal、Samik Bindu、Sumanta Dey、Athar Alam、Manish Goyal、Mohd. Shameel Iqbal、Souvik Sarkar、Rahul Kumar、Kamal Krishna Halder、Mita Chatterjee Debnath、Susanta Adhikari、Uday Bandyopadhyay

  DOI：10.1074/jbc.m111.307199

  日期：2012.1

  We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.