(Z,Z,Z,Z,Z,Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-docosa-4,7,10,13,16,19-hexaenamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (Z,Z,Z,Z,Z,Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-docosa-4,7,10,13,16,19-hexaenamide
• 英文别名: N-docosahexaenoyl vanillylamine；dohevanil；(4Z,7Z,10Z,13Z,16Z,19Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]docosa-4,7,10,13,16,19-hexaenamide
• 化学式: C₃₀H₄₁NO₃
• 分子量: 463.66
• InChiKey: IFFDMDPMYLRJPN-JDPCYWKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  34
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  二十二碳六烯酸 、 香兰素胺盐酸盐 在 三乙胺 作用下， 反应 48.0h， 以54%的产率得到(Z,Z,Z,Z,Z,Z)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-docosa-4,7,10,13,16,19-hexaenamide
  参考文献：
  名称：

  衍生自n-3多不饱和脂肪酸（PUFA）的辣椒素类似物可降低巨噬细胞的炎症活性并通过β细胞体外刺激胰岛素分泌。

  摘要：

  在这项研究中，从相应的n-3长链多不饱和脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）酶促合成了两个辣椒素类似物N-二十碳五烯酰基香草醛胺（EPVA）和N-二十二碳六烯酰基香草醛胺（DHVA），这两个饮食都与饮食有关。这些化合物可通过RAW264显着减少某些脂多糖（LPS）诱导的炎症介质的产生，包括一氧化氮（NO），巨噬细胞炎症蛋白3α（CCL20）和单核细胞趋化蛋白1（MCP-1或CCL2）。 7个巨噬细胞。其次，只有EPVA可以增加胰腺INS-1 832/13β细胞的胰岛素分泌，同时提高细胞内Ca2 +和ATP的浓度。这表明胰岛素释放的刺激通过在第一阶段中细胞内ATP / ADP比的增加而发生，而在第二阶段中是钙介导的。尽管尚不知道内源性产生EPVA，但其在糖尿病治疗中的潜在治疗价值值得进一步研究。

  DOI：

  10.3390/nu11040915

文献信息

• Evaluation of endogenous fatty acid amides and their synthetic analogues as potential anti-inflammatory leads
  作者：Hung The Dang、Gyeoung Jin Kang、Eun Sook Yoo、Jongki Hong、Jae Sue Choi、Hyung Sik Kim、Hae Young Chung、Jee H. Jung

  DOI：10.1016/j.bmc.2010.12.046

  日期：2011.2

  A series of endogenous fatty acid amides and their analogues (1-78) were prepared, and their inhibitory effects on pro-inflammatory mediators (NO, IL-1 beta, IL-6, and TNF-alpha) in LPS-activated RAW264.7 cells were evaluated. Their inhibitory activity on the pro-inflammatory chemokine MDC in IFN-gamma-activated HaCaT cells was also examined. The results showed that the activity is strongly dependent on the nature of the fatty acid part of the molecules. As expected, the amides derived from enone fatty acids showed significant activity and were more active than those derived from other types of fatty acids. A variation of the amine headgroup also altered bioactivity profile remarkably, possibly by modulating cell permeability. Regarding the amine part of the molecules, N-acyl dopamines exhibited the most potent activity (IC50 similar to 2 mu M). This is the first report of the inhibitory activity of endogenous fatty acid amides and their analogues on the production of nitric oxide, cytokines (IL-1 beta, IL-6, and TNF-alpha) and the chemokine MDC. This study suggests that the enone fatty acid-derived amides (such as N-acyl ethanolamines and N-acyl amino acids) and N-acyl dopamines may be potential anti-inflammatory leads. (C) 2010 Elsevier Ltd. All rights reserved.
• Apoptosis induction by dohevanil, a DHA substitutive analog of capsaicin, in MCF-7 cells
  作者：Tuoya、Naomichi Baba、Yasuaki Shimoishi、Yoshiyuki Murata、Mikiro Tada、Masamichi Koseki、Kyoya Takahata

  DOI：10.1016/j.lfs.2005.07.019

  日期：2006.2

  Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a major pungent ingredient in a variety of red peppers of the genus Capsicum, is a type of vanilloid. It has been shown to induce apoptosis in many cell types. The effects of vanilloids on apoptosis induction are thought to be correlated with the length and degree of the unsaturation of the fatty acyl chains, In this Study, we compared the effect of capsaicin and its docosahexaenoic acid (DHA, C22:6) analog (we named as dohevanil) on human breast cancer MCF-7 cells, which do not express caspase-3. Dohevanil, which was synthesized from DHA and vanillylamine, has longer and highly unsaturated fatty acyl chain than capsaicin. We showed that both vanilloids exhibit effects of growth inhibition and DNA fragmentation induction in MCF-7 cells. These effects of dohevanil were more potent than capsaicin. Because these effects were inhibited by z-VAD-fmk, 1 broad-spectrum caspase inhibitor, the vanilloids induced the apoptosis via caspase-dependent pathway not involving caspase-3. In conclusion, dohevanil has I more potent effect on apoptosis induction in MCF-7 cells than capsaicin. (c) 2005 Elsevier Inc. All rights reserved.
• Capsaicin Analogues Derived from n-3 Polyunsaturated Fatty Acids (PUFAs) Reduce Inflammatory Activity of Macrophages and Stimulate Insulin Secretion by β-Cells In Vitro
  作者：Erika Cione、Pierluigi Plastina、Attilio Pingitore、Mariarita Perri、Maria Cristina Caroleo、Alessia Fazio、Renger Witkamp、Jocelijn Meijerink

  DOI：10.3390/nu11040915

  日期：——

  In this study, two capsaicin analogues, N-eicosapentaenoyl vanillylamine (EPVA) and N-docosahexaenoyl vanillylamine (DHVA), were enzymatically synthesized from their corresponding n-3 long chain polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both dietary relevant components. The compounds significantly reduced the production of some lipopolysaccharide (LPS)-induced

  在这项研究中，从相应的n-3长链多不饱和脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）酶促合成了两个辣椒素类似物N-二十碳五烯酰基香草醛胺（EPVA）和N-二十二碳六烯酰基香草醛胺（DHVA），这两个饮食都与饮食有关。这些化合物可通过RAW264显着减少某些脂多糖（LPS）诱导的炎症介质的产生，包括一氧化氮（NO），巨噬细胞炎症蛋白3α（CCL20）和单核细胞趋化蛋白1（MCP-1或CCL2）。 7个巨噬细胞。其次，只有EPVA可以增加胰腺INS-1 832/13β细胞的胰岛素分泌，同时提高细胞内Ca2 +和ATP的浓度。这表明胰岛素释放的刺激通过在第一阶段中细胞内ATP / ADP比的增加而发生，而在第二阶段中是钙介导的。尽管尚不知道内源性产生EPVA，但其在糖尿病治疗中的潜在治疗价值值得进一步研究。