咖啡酸苯乙酯酰化衍生物的设计、合成及其作为抗氧化应激损伤的中枢神经保护剂的活性评估

doi:10.5246/jcps.2013.06.069

中国药学(英文版)

咖啡酸苯乙酯酰化衍生物的设计、合成及其作为抗氧化应激损伤的中枢神经保护剂的活性评估

朱仁宗, 宁显玲, 张志丽, 王孝伟, 田超, 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:2013-06-03 修回日期:2013-06-15 出版日期:2013-11-15 发布日期:2014-01-22
通讯作者: 刘俊义*

Design, synthesis and pharmacological evaluation of caffeic acid phenethyl ester acylation as multifunctional neuroprotective agents against oxidative stress injury

Renzong Zhu, Xianling Ning, Zhili Zhang, Xiaowei Wang, Chao Tian, Junyi Liu^*

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

Received:2013-06-03 Revised:2013-06-15 Online:2013-11-15 Published:2014-01-22
Contact: Junyi Liu*

摘要/Abstract

摘要：

以咖啡酸苯乙酯(CAPE)为先导物, 将其对位酚羟基或间位、对位两个酚羟基进行酰化, 制备CAPE的前药, 提高其稳定性和脂溶性。并采用了H2O2和6-OHDA两种模型对其进行了神经保护活性测定。结果显示目标化合物相较于CAPE能够更好地保护PC12神经细胞免受氧化应激损伤。此外, 目标化合物也显示出了较强的血脑屏障透过能力。

关键词: 肌萎缩侧索硬化症, 酰化(产物)反应, 咖啡酸苯乙酯, 神经保护剂, 血脑屏障透过率

Abstract:

4-Acylated or 3,4-diacylated caffeic acid phenethyl ester (CAPE) was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H2O2 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.

Key words: Amyotrophic lateral sclerosis, Acylation, Caffeic acid phenethyl ester, Neuroprotective agents, Blood-brain barrier permeability

中图分类号:

R916

Supporting:

Foundation item: National Natural Science Foundation of China (Grant No. 201310061931.8).#br# ^*Corresponding author. Tel.: 86-10-82805203

朱仁宗, 宁显玲, 张志丽, 王孝伟, 田超, 刘俊义^*. 咖啡酸苯乙酯酰化衍生物的设计、合成及其作为抗氧化应激损伤的中枢神经保护剂的活性评估[J]. 中国药学(英文版), DOI: 10.5246/jcps.2013.06.069.

Renzong Zhu, Xianling Ning, Zhili Zhang, Xiaowei Wang, Chao Tian, Junyi Liu^*. Design, synthesis and pharmacological evaluation of caffeic acid phenethyl ester acylation as multifunctional neuroprotective agents against oxidative stress injury[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2013.06.069.

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咖啡酸苯乙酯酰化衍生物的设计、合成及其作为抗氧化应激损伤的中枢神经保护剂的活性评估

Design, synthesis and pharmacological evaluation of caffeic acid phenethyl ester acylation as multifunctional neuroprotective agents against oxidative stress injury

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