n-hexadecanyl caffeate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: n-hexadecanyl caffeate
• 英文别名: caffeic acid n-hexadecyl ester；hexadecyl caffeate；(E)-hexadecyl 3-(3,4-dihydroxyphenyl)acrylate；(E)-hexadecyl 3-(3,4-dihydroxyphenyl)propenoate；trans-hexadecyl 3-(3,4-dihydroxyphenyl)propenoate；caffeic acid hexadecyl ester；n-hexadecyl caffeate；hexadecyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
• 化学式: C₂₅H₄₀O₄
• 分子量: 404.59
• InChiKey: VPDDQCXWJMAIAY-HTXNQAPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10
• 重原子数：
  29
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  TRANS-咖啡酸 在 吡啶 、 4-二甲氨基吡啶 、 草酰氯 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 n-hexadecanyl caffeate
  参考文献：
  名称：

  Antioxidant activity of olive phenols: mechanistic investigation and characterization of oxidation products by mass spectrometry

  摘要：

  在本研究中，首先通过它们的化学计量学ntot（每个抗氧化剂分子捕获的自由基数量）和稳定自由基DPPH的第一个H原子抽提反应速率常数k1，来表征橄榄多酚的抗氧化活性。结果显示，橄榄苦苷、羟基酪醇和咖啡酸具有最大的k1值，而咖啡酸的肠道代谢物二羟基咖啡酸在ntot方面是最优秀的抗氧化剂。对于含有邻苯二酚基团的多酚，ntot值高于二，这意味着它们初始形成的氧化产物具有抗氧化效果。通过高效液相色谱-质谱（HPLC-MS）分析，在AAPH诱导的橄榄多酚氧化过程中形成的主要产物显示出二聚体和三聚体的存在。在羟基酪醇和二羟基咖啡酸的情况下，聚合反应伴随着水分子的加入。 然后，通过它们抑制AAPH诱导SDS胶束中亚油酸过氧化的能力来评估橄榄多酚的抗氧化活性。结果表明，橄榄多酚和槲皮素作为延缓剂而非链断裂剂如α-生育酚。通过详细的机理研究，发现橄榄多酚抑制脂质过氧化的作用可以通过假设它们基本减少AAPH衍生出的引发自由基来满意地解释。总体而言，橄榄多酚证明是有效的亲水性过氧自由基清除剂，由于其氧化产物中一些残余的活性，具有持久的抗氧化效果。

  DOI：

  10.1039/b416101g

文献信息

• Antioxidant activity of olive phenols: mechanistic investigation and characterization of oxidation products by mass spectrometry
  作者：Marjolaine Roche、Claire Dufour、Nathalie Mora、Olivier Dangles

  DOI：10.1039/b416101g

  日期：——

  In this work, the antioxidant activity of olive phenols is first characterized by their stoichiometries ntot (number of radicals trapped per antioxidant molecule) and their rate constants for the first H-atom abstraction k1 by the stable radical DPPH. It appears that oleuropein, hydroxytyrosol and caffeic acid have the largest k1 values, whereas dihydrocaffeic acid, an intestinal metabolite of caffeic acid, is the best antioxidant in terms of ntot. For phenols with a catechol moiety ntot is higher than two, implying an antioxidant effect of their primarily formed oxidation products. A HPLC–MS analysis of the main products formed in the AAPH-induced oxidation of olive phenols reveals the presence of dimers and trimers. With hydroxytyrosol and dihydrocaffeic acid, oligomerization can take place with the addition of water molecules. The antioxidant activity of olive phenols is then evaluated by their ability to inhibit the AAPH-induced peroxidation of linoleic acid in SDS micelles. It is shown that olive phenols and quercetin act as retardants rather than chain breakers like α-tocopherol. From a detailed mechanistic investigation, it appears that the inhibition of lipid peroxidation by olive phenols can be satisfactorily interpreted by assuming that they essentially reduce the AAPH-derived initiating radicals. Overall, olive phenols prove to be efficient scavengers of hydrophilic peroxyl radicals with a long lasting antioxidant effect owing to the residual activity of some of their oxidation products.

  在本研究中，首先通过它们的化学计量学ntot（每个抗氧化剂分子捕获的自由基数量）和稳定自由基DPPH的第一个H原子抽提反应速率常数k1，来表征橄榄多酚的抗氧化活性。结果显示，橄榄苦苷、羟基酪醇和咖啡酸具有最大的k1值，而咖啡酸的肠道代谢物二羟基咖啡酸在ntot方面是最优秀的抗氧化剂。对于含有邻苯二酚基团的多酚，ntot值高于二，这意味着它们初始形成的氧化产物具有抗氧化效果。通过高效液相色谱-质谱（HPLC-MS）分析，在AAPH诱导的橄榄多酚氧化过程中形成的主要产物显示出二聚体和三聚体的存在。在羟基酪醇和二羟基咖啡酸的情况下，聚合反应伴随着水分子的加入。 然后，通过它们抑制AAPH诱导SDS胶束中亚油酸过氧化的能力来评估橄榄多酚的抗氧化活性。结果表明，橄榄多酚和槲皮素作为延缓剂而非链断裂剂如α-生育酚。通过详细的机理研究，发现橄榄多酚抑制脂质过氧化的作用可以通过假设它们基本减少AAPH衍生出的引发自由基来满意地解释。总体而言，橄榄多酚证明是有效的亲水性过氧自由基清除剂，由于其氧化产物中一些残余的活性，具有持久的抗氧化效果。
• Synthesis and antioxidant activity of long chain alkyl hydroxycinnamates
  作者：Jose C.J.M.D.S. Menezes、Shrivallabh P. Kamat、Jose A.S. Cavaleiro、Alexandra Gaspar、Jorge Garrido、Fernanda Borges

  DOI：10.1016/j.ejmech.2010.12.016

  日期：2011.2

  Long chain alkyl hydroxycinnamates (8–21) were synthesized from the corresponding half esters of malonic acid (5–7) and benzaldehyde derivatives by Knoevenagel condensation. The total antioxidant capacity of these hydroxycinnamyl esters was evaluated using DPPH and ABTS assays. The observed antioxidant activity was highest for esters of caffeic acid followed by sinapic esters and ferulic esters. The

  长链烷基羟基肉桂酸酯（8 – 21）是由丙二酸的相应半酯（5 – 7）合成的）与苯甲醛衍生物经Knoevenagel缩合。使用DPPH和ABTS分析评估了这些羟基肉桂酸酯的总抗氧化能力。观察到的抗氧化剂活性最高的是咖啡酸酯，其次是芥子酸酯和阿魏酸酯。这些羟基肉桂酸酯的类药性参数也根据L​​ipinski的“五则规则”进行了评估。发现所有酯衍生物均违反了Lipinski的参数之一（cLogP> 5），即使已发现它们可溶于质子溶剂中。预测的拓扑极性表面积（TPSA）数据可以得出结论，它们可以具有良好的穿透细胞膜的能力。因此，可以提出这些新颖的亲脂性化合物作为用于应对氧化过程的潜在抗氧化剂。
• Long Chain Alkyl Esters of Hydroxycinnamic Acids as Promising Anticancer Agents: Selective Induction of Apoptosis in Cancer Cells
  作者：José C. J. M. D. S. Menezes、Najmeh Edraki、Shrivallabh P. Kamat、Mahsima Khoshneviszadeh、Zahra Kayani、Hossein Hadavand Mirzaei、Ramin Miri、Nasrollah Erfani、Maryam Nejati、José A. S. Cavaleiro、Tiago Silva、Luciano Saso、Fernanda Borges、Omidreza Firuzi

  DOI：10.1021/acs.jafc.7b01388

  日期：2017.8.23

  alkyl esters may possess enhanced biological activities. We evaluated C4, C14, C16, and C18 alkyl esters of p-coumaric, ferulic, sinapic, and caffeic acids (19 compounds) for their cytotoxic activity against four human cancer cells and also examined their effect on cell cycle alteration and apoptosis induction. The tetradecyl (1c) and hexadecyl (1d) esters of p-coumaric acid and tetradecyl ester of caffeic

  癌症是全世界发病率和死亡率的主要原因。羟基肉桂酸（HCA）是天然存在的化合物，其烷基酯可能具有增强的生物活性。我们评估了对香豆酸，阿魏酸，芥子酸和咖啡酸（19种化合物）的C4，C14，C16和C18烷基酯对四种人类癌细胞的细胞毒活性，并且还研究了它们对细胞周期改变和凋亡诱导的影响。对香豆酸的十四烷基（1c）和十六烷基（1d）和咖啡酸（4c）的十四烷基酯（而非亲本的HCA）具有IC 50对MOLT-4（人淋巴细胞白血病）细胞的选择性作用。分别为0.123±0.012、0.301±0.069和1.0±0.1μM。化合物1c，1d和4c显着增加了亚G1期的凋亡细胞，并激活了MOLT-4细胞中的caspase-3酶。化合物1c对抗药性MES-SA-DX5子宫肉瘤细胞的效力分别比阿霉素和顺铂高15.4倍和23.6倍。这些对香豆酸酯对NIH / 3T3成纤维细胞的功效要低好几倍。对接研究表明1c可能通
• Selective antiproliferative activity of caffeic acid phenethyl ester analogues on highly liver-Metastatic murine colon 26-L5 carcinoma cell line
  作者：T Nagaoka

  DOI：10.1016/s0968-0896(02)00138-4

  日期：2002.10

  Caffeic acid phenethyl ester (CAPE, 2) and its twenty analogues (1, 3-21) were prepared. These esters were tested by MTT assay on growth of murine colon 26-L5 carcinoma, murine B16-BL6 malonoma, murine Lewis lung carcinoma, human HT-1080 fibrosarcoma, human lung A549 adenocarcinoma, and human cervix HeLa adenocarcinoma cell lines. It was found that CAPE analogues possessed selective antiproliferative activity toward highly liver-metastatic murine colon 26-L5 carcinoma cell line. Among them, 4-phenylbutyl caffeate (4), (Z)-8-phenyl-7-octenyl (10a) and (E)-8-phenyl-7-octenyl (10b) caffeate showed the most potent antiproliferative activity (EC50 value, 0.02 muM). In addition, CAPE (2) induced DNA fragmentation at concentrations of 1 to 10 mug/mL towards murine colon 26-L5 carcinoma cells. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Impact of Alkyl Esters of Caffeic and Ferulic Acids on Tumor Cell Proliferation, Cyclooxygenase Enzyme, and Lipid Peroxidation
  作者：Bolleddula Jayaprakasam、Mulabagal Vanisree、Yanjun Zhang、David L. Dewitt、Muraleedharan G. Nair

  DOI：10.1021/jf060899p

  日期：2006.7.1

  The antioxidant ferulic and caffeic acid phenolics are ubiquitous in plants and abundant in fruits and vegetables. We have synthesized a series of ferulic and caffeic acid esters and tested for tumor cell proliferation, cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation inhibitory activities in vitro. In the tumor cell proliferation assay, some of these esters showed excellent growth inhibition of colon cancer cells. Among the phenolics esters assayed, compounds 10 (C-12-caffeate), 11 (C-16-caffeate), 21 (C-8-ferulate), and 23 (C-12-ferulate) showed strong growth inhibition with IC50 values of 16.55, 13.46, 18.67, and 7.57 mu g/mL in a breast cancer cell line; 9.65, 7.45, 17.05, and 4.35 mu g/mL in a lung cancer cell line; 5.78, 3.5, 4.29, and 2.46 mu g/mL in a colon cancer cell line; 12.04, 12.21, 14.63, and 8.09 mu g/mL in a central nervous system cancer cell line; and 8.62, 7.76, 11.0, and 5.37 in a gastric cancer cell line. In COX enzyme inhibitory assays, ferulic and caffeic acid esters significantly inhibited both COX-1 and COX-2 enzymes. Caffeates 5-10 (C-4-C-12), inhibited COX-1 enzyme between 50% and 90% and COX-2 enzyme by about 70%, whereas ferulates 15-21 (C-3-C-8) inhibited COX-1 and COX-2 enzymes by 85-95% 25 mu g/mL. Long-chain caffeates 11-14 (C-16-C-22) and short-chain ferulates 15-20 (C-3-C-5) were the most active in lipid peroxidation inhibition and showed 6070% activity at 5 mu g/mL concentration.