16,17-epoxydocosapentaenoic acid | 895127-63-6

• 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: 16,17-epoxydocosapentaenoic acid
• 英文别名: 16(17)-EpDPE；(4Z,7Z,10Z,13Z)-15-[3-[(Z)-pent-2-enyl]oxiran-2-yl]pentadeca-4,7,10,13-tetraenoic acid
• CAS: 895127-63-6
• 化学式: C₂₂H₃₂O₃
• 分子量: 344.494
• InChiKey: BCTXZWCPBLWCRV-ZYADFMMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  16,17-epoxydocosapentaenoic acid 、 C.I.酸性橙108 在 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 0.33h， 生成 (4Z,7Z,10Z,13Z)-N-(2-hydroxyethyl)-15-[3-[(Z)-pent-2-enyl]oxiran-2-yl]pentadeca-4,7,10,13-tetraenamide
  参考文献：
  名称：

  Antitumorigenic Properties of Omega-3 Endocannabinoid Epoxides

  摘要：

  Accumulating studies have linked inflammation to tumor progression. Dietary omega-3 fatty acids, such as docosahexaenoic acid (DHA), have been shown to suppress tumor growth through their conversion to epoxide metabolites. Alternatively, DHA is converted enzymatically into docosahexaenoylethanolamide (DHEA), an endocannabinoid with antiproliferative activity. Recently, we reported a novel class of anti-inflammatory DHEA-epoxide derivative called epoxydocospentaenoic-ethanolamide (EDP-EA) that contain both ethanolamide and epoxide moieties. Herein, we study the antitumorigenic properties of EDP-EAs in an osteosarcoma (OS) model. First, we show similar to 80% increase in EDP-EAs in metastatic versus normal lungs of mice. We found significant differences in the apoptotic and antimigratory potencies of the different EDPEA regioisomers, which were partially mediated through cannabinoid receptor 1 (CB1). Next, we synthesized derivatives of the most pro-apoptotic regioisomer. These derivatives had reduced hydrolytic susceptibility to fatty acid amide hydrolase (FAAH) and increased CB1-selective binding. Collectively, we report a novel class of EDP-EAs that exhibit antiangiogenic, antitumorigenic, and antimigratory properties in OS.

  DOI：

  10.1021/acs.jmedchem.8b00243
• 作为产物：
  描述：

  二十二碳六烯酸 在 CYP₁₀₂A₁ F₈₇V 、 magnesium chloride 作用下， 以63%的产率得到cis-14,15-epoxyeicosatrienoic acid
  参考文献：
  名称：

  Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450

  摘要：

  Cytochromes P450 (CYPs) metabolize polyunsaturated long-chain fatty acids (PUFA-LC) to several classes of oxygenated metabolites. Through use of human recombinant CYPs, we recently showed that CYP1A1, -2C19, -2D6, -2E1, and -3A4 are mainly hydroxylases, whereas CYP1A2, -2C8, -2C9, and -2J2 are mainly epoxygenases of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. It is worth noting that the last double bond of these PUFAs, i.e., omega 6 in AA or omega 3 in EPA and DHA, respectively, was preferentially epoxidized. In this study, we have characterized the stereoselectivity of this epoxidation reaction by comparison with the PUFA-LC epoxide stereoisomers obtained from the enantioselective bacterial CYP102A1 F87V. The stereoselectivity of the epoxidation of the last olefin of AA (omega 6), EPA (omega 3), or DHA (omega 3) differed between the CYP isoforms but was similar for EPA and DHA. These data give additional insight into the PUFA-LC epoxide enantiomers generated by the hepatic CYPs.-Lucas, D., S. Goulitquer, J. Marienhagen, M. Fer, Y. Dreano, U. Schwaneberg, Y. Amet, and L. Corcos. Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J. Lipid Res. 2010. 51: 1125-1133.

  DOI：

  10.1194/jlr.m003061

文献信息

• VANROLLINS, MIKE;FRADE, PETER D.;CARRETERO, OSCAR A., J. LIPID RES., 30,(1989) N, C. 275-286
  作者：VANROLLINS, MIKE、FRADE, PETER D.、CARRETERO, OSCAR A.

  DOI：——

  日期：——
• STABLE ANALOGS OF CYP450 LIPID METABOLITES AND INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE
  申请人：Massachusetts Eye & Ear Infirmary

  公开号：EP3377056B1

  公开（公告）日：2020-09-23
• Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450
  作者：Danièle Lucas、Sophie Goulitquer、Jan Marienhagen、Maude Fer、Yvonne Dreano、Ulrich Schwaneberg、Yolande Amet、Laurent Corcos

  DOI：10.1194/jlr.m003061

  日期：2010.5

  Cytochromes P450 (CYPs) metabolize polyunsaturated long-chain fatty acids (PUFA-LC) to several classes of oxygenated metabolites. Through use of human recombinant CYPs, we recently showed that CYP1A1, -2C19, -2D6, -2E1, and -3A4 are mainly hydroxylases, whereas CYP1A2, -2C8, -2C9, and -2J2 are mainly epoxygenases of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. It is worth noting that the last double bond of these PUFAs, i.e., omega 6 in AA or omega 3 in EPA and DHA, respectively, was preferentially epoxidized. In this study, we have characterized the stereoselectivity of this epoxidation reaction by comparison with the PUFA-LC epoxide stereoisomers obtained from the enantioselective bacterial CYP102A1 F87V. The stereoselectivity of the epoxidation of the last olefin of AA (omega 6), EPA (omega 3), or DHA (omega 3) differed between the CYP isoforms but was similar for EPA and DHA. These data give additional insight into the PUFA-LC epoxide enantiomers generated by the hepatic CYPs.-Lucas, D., S. Goulitquer, J. Marienhagen, M. Fer, Y. Dreano, U. Schwaneberg, Y. Amet, and L. Corcos. Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J. Lipid Res. 2010. 51: 1125-1133.
• Antitumorigenic Properties of Omega-3 Endocannabinoid Epoxides
  作者：Jahnabi Roy、Josephine E. Watson、In Sup Hong、Timothy M. Fan、Aditi Das

  DOI：10.1021/acs.jmedchem.8b00243

  日期：2018.7.12

  Accumulating studies have linked inflammation to tumor progression. Dietary omega-3 fatty acids, such as docosahexaenoic acid (DHA), have been shown to suppress tumor growth through their conversion to epoxide metabolites. Alternatively, DHA is converted enzymatically into docosahexaenoylethanolamide (DHEA), an endocannabinoid with antiproliferative activity. Recently, we reported a novel class of anti-inflammatory DHEA-epoxide derivative called epoxydocospentaenoic-ethanolamide (EDP-EA) that contain both ethanolamide and epoxide moieties. Herein, we study the antitumorigenic properties of EDP-EAs in an osteosarcoma (OS) model. First, we show similar to 80% increase in EDP-EAs in metastatic versus normal lungs of mice. We found significant differences in the apoptotic and antimigratory potencies of the different EDPEA regioisomers, which were partially mediated through cannabinoid receptor 1 (CB1). Next, we synthesized derivatives of the most pro-apoptotic regioisomer. These derivatives had reduced hydrolytic susceptibility to fatty acid amide hydrolase (FAAH) and increased CB1-selective binding. Collectively, we report a novel class of EDP-EAs that exhibit antiangiogenic, antitumorigenic, and antimigratory properties in OS.