cis-eicosa-5,8,11,14,17-pentaenoic acid (3-hydroxy propyl)amide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: cis-eicosa-5,8,11,14,17-pentaenoic acid (3-hydroxy propyl)amide
• 英文别名: (5Z,8Z,11Z,14Z,17Z)-N-(3-hydroxypropyl)icosa-5,8,11,14,17-pentaenamide
• 化学式: C₂₃H₃₇NO₂
• 分子量: 359.552
• InChiKey: LOSPJEDAOQMATF-JLNKQSITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  EPA乙酯 、 3-氨基-1-丙醇 以 neat (no solvent) 为溶剂， 反应 24.0h， 以57%的产率得到cis-eicosa-5,8,11,14,17-pentaenoic acid (3-hydroxy propyl)amide
  参考文献：
  名称：

  Synthesis and discovery of ω-3 polyunsaturated fatty acid- alkanolamine (PUFA-AA) derivatives as anti-inflammatory agents targeting Nur77

  摘要：

  In this work, three series of ω-3 polyunsaturated fatty acid-alkanolamine derivatives (PUFA-AAs) were synthesized, characterized and their anti-inflammatory activity in vivo was evaluated. Compounds 4a, 4f, and 4k exhibited marked anti-inflammatory activity in LPS-stimulated RAW 264.7 cells. The most promising compound 4k dose-dependently suppressed the cytokines with IC₅₀ values in the low micromolar range. Further, 4k exhibited potential in vitro Nur77-binding affinity (K_d = 6.99 × 10^-6 M) which is consistent with the result of docking studies. Next, the anti-inflammatory mechanism of 4k was found to be through NF-κB signal pathway in a Nur77-dependent manner. Moreover, we also observed 4k significantly inhibited LPS-induced expression of cytokines (IL-6, TNF-α, and IL-1β) through suppressing NF-κB activation and attenuated LPS-induced inflammation in mouse acute lung injury (ALI) model. In conclusion, the study strongly suggests that the PUFA-AA derivatives can be particularly as new Nur77 mediators for further treatment in inflammatory diseases.

  DOI：

  10.1016/j.bioorg.2020.104456

文献信息

• Synthesis and discovery of ω-3 polyunsaturated fatty acid- alkanolamine (PUFA-AA) derivatives as anti-inflammatory agents targeting Nur77
  作者：Hua Fang、Jianyu Zhang、Mingtao Ao、Fengming He、Weizhu Chen、Yuqing Qian、Yuxiang Zhang、Yang Xu、Meijuan Fang

  DOI：10.1016/j.bioorg.2020.104456

  日期：2020.12

  In this work, three series of ω-3 polyunsaturated fatty acid-alkanolamine derivatives (PUFA-AAs) were synthesized, characterized and their anti-inflammatory activity in vivo was evaluated. Compounds 4a, 4f, and 4k exhibited marked anti-inflammatory activity in LPS-stimulated RAW 264.7 cells. The most promising compound 4k dose-dependently suppressed the cytokines with IC₅₀ values in the low micromolar range. Further, 4k exhibited potential in vitro Nur77-binding affinity (K_d = 6.99 × 10^-6 M) which is consistent with the result of docking studies. Next, the anti-inflammatory mechanism of 4k was found to be through NF-κB signal pathway in a Nur77-dependent manner. Moreover, we also observed 4k significantly inhibited LPS-induced expression of cytokines (IL-6, TNF-α, and IL-1β) through suppressing NF-κB activation and attenuated LPS-induced inflammation in mouse acute lung injury (ALI) model. In conclusion, the study strongly suggests that the PUFA-AA derivatives can be particularly as new Nur77 mediators for further treatment in inflammatory diseases.