(1E)-2-(3',4'-二羟基苯基)乙烯磺酸苯酯类神经保护剂的合成及活性评估

(1E)-2-(3',4'-二羟基苯基)乙烯磺酸苯酯类神经保护剂的合成及活性评估

陈柱佗, 宁显玲, 刘俊义^*

北京大学医学部药学院化学生物学系, 北京 100191

收稿日期:2012-12-11 修回日期:2013-02-10 出版日期:2013-03-18 发布日期:2013-03-18
通讯作者: 刘俊义*

Synthesis of (1E)-phenyl-2-(3',4'-dihydroxyphenyl)ethenesulfonates as potent neuroprotective agents and evaluation of their activities

Zhutuo Chen, Xianling Ning, Junyi Liu^*

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2012-12-11 Revised:2013-02-10 Online:2013-03-18 Published:2013-03-18
Contact: Junyi Liu*

摘要/Abstract

摘要： 本文以咖啡酸苯乙酯为先导物设计合成了一系列 (1E)-2-(3',4'-二羟基苯基)乙烯磺酸苯酯类化合物作为抗肌萎缩侧索硬化症的药物, 并对其神经保护作用进行了活性评估, 结果表明将咖啡酸苯乙酯的羧酸酯结构替换成磺酸酯结构后, 在LPS诱导BV2细胞产生炎症测定药物神经保护活性的模型中, 化合物的活性没有明显提高; 在过氧化氢H2O2诱导PC12细胞氧化损伤测定药物神经保护活性的模型中, 所合成的化合物神经保护作用与咖啡酸苯乙酯处于同一水平。

关键词: 咖啡酸苯乙酯, 乙烯磺酸苯酯, 神经保护

Abstract:

A series of (1E)-phenyl-2-(3',4'-dihydroxyphenyl)ethenesulfonate derivatives were designed and synthesized as anti-amyotrophic lateral sclerosis (ALS) agents, based on the lead compound caffeic acid phenethyl ester (CAPE). And their neuroprotective activities were evaluated. The results indicated that replacement of the carboxylic ester by sulfonic ester did not produce better neuroprotective activity in the model of LPS induced inflammation in BV2 cells. However, the results in the model of H2O2 induced damage in PC12 cells showed that the neuroprotective activities of all the target compounds and CAPE were about the same.

Key words: Caffeic acid phenethyl ester, Phenylethene sulfonate, Neuroprotection

中图分类号:

R916

Supporting: Foundation items: National Natural Science Foundation of China (Grant No. 20972011, 21042009, 21172014).
^*Corresponding author. Tel.: 86-10-82801706

陈柱佗, 宁显玲, 刘俊义^*. (1E)-2-(3',4'-二羟基苯基)乙烯磺酸苯酯类神经保护剂的合成及活性评估[J]. .

Zhutuo Chen, Xianling Ning, Junyi Liu^*. Synthesis of (1E)-phenyl-2-(3',4'-dihydroxyphenyl)ethenesulfonates as potent neuroprotective agents and evaluation of their activities[J]. .

参考文献

[1] Gros-Louis, F.; Gaspar, C.; Rouleau, G.A. Biochim. Biophys. Acta. 2006, 1762, 956-972.
[2] McCord, J.M. Science. 1994. 266, 1586-1587.
[3] Andersen, P.M.; Sims, K.B.; Xin, W.W.; Kiely, R.; O’Neill, G.; Ravits, J.; Pioro, E.; Harati, Y.; Brower, R.D.; Levine, J.S.; Heinicke, H.U.; Seltzer, W.; Boss, M.; Brown, R.H.Jr. Amyotroph Lateral Scler. Other Motor. Neuron. Disord. 2003, 4, 62-73.
[4] Zagami, C.J.; Beart, P.M.; Wallis, N. Glia. 2009, 57, 119-135.
[5] Trotti, D.; Rolfs, A.; Danbolt, N.C.; Brown, R.H.; Hediger, M.A. Nat. Neurosci. 1999, 2, 848.
[6] Gibb, S.L.; Boston-Howes, W.; Lavina, Z.S.; Gustincich, S.; Robert, H.B.Jr.; Pasinelli, P.; Trotti, D. J. Biol. Chem. 2007, 282, 32480-32490.
[7] Pasinelli, P.; Brown, R.H. Nat. Rev. Neurosci. 2006, 7, 710-723.
[8] Mallireddigari, M.R.; Pallela,V.R.; Reddy, E.P. Synthesis. 2005, 20, 3639-3643.
[9] Wei, X.; Zhao, L.; Ma, Z.; Holtzman, D.M.; Yan, C.; Dodel, R.C.; Hampel, H.; Oertel, W.; Farlow, M.R.; Du, Y. Brain. 2004, 127, 2629-2635.
[10] Noelker, C.; Bacher, M.; Gocke, P.; Wei, X.; Klockgether, T.; Du, Y.; Dodel, R. Neurosci. Lett. 2005, 383, 39-43.
[11] Carretero, J.C.; Demillequand, M.; Ghosez, L. Tetrahedron. 1987, 21, 5125-5134.
[12] Shealy, Y.F.; Krauth, C.A.; Struck, R.F.; Montgomery, J.A. J. Med. Chem. 1983, 26, 1168-1173.
[13] Lee, Y.Z.; Yang, C.W.; Kang, I.J.; Wu, S.H.; Chao, Y.S.; Chern, J.H.; Lee, S.J. Bioorg. Med. Chem. Lett. 2008. 18, 5676-5679.
[14] Kiaei, M.K.; Lee, K.; Petri, S.; Choi, D.K.; Chen, J.Y.; Calingasan, N.Y.; Beal, M.F. J. Neurochem. 2005, 93, 403-411.
[15] Choi, Y.; Lee, M.K.; Lim, S.Y.; Sung, S.H.; Kim, Y.C. Br. J. Pharmacol. 2009, 156, 933-940.
[16] Ma, Z.Z.; Xing, W.; Fontanilla, C.; Noelker, C.; Dodel, R.; Hampel, H.; Du, Y.S. Life Sci. 2006, 79, 1307-1311.
[17] Kim, S.E.; Yoon, H.; Nam, T.G.; Heo, H.J.; Lee, C.Y.; Kim, D.O. J. Med. Food. 2010, 13, 779-784.
[18] Olas, B.; Wachowicz, B.; Saluk-Juszczak, J.; Zielinski, T.; Kaca, W.; Buczynski, A. Cell Biol. Toxicol. 2001, 17, 117-125.