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

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(英文)

作　　者：朱仁宗[1] 宁显玲[1] 张志丽[1] 王孝伟[1] 田超[1] 刘俊义[1] 

机构地区：[1]北京大学医学部 药学院 化学生物学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2013年第6期475-482,共8页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.201310061931.8)

摘　　要：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 H202 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC 12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.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：Amyotrophic lateral sclerosis ACYLATION Caffeic acid phenethyl ester Neuroprotective agents Blood-brain barrier permeability 

分 类 号：R914[医药卫生—药物化学]