摘要/Abstract

设计、合成了一系列新型吡喃并[2，3-b]萘醌类衍生物.抗胆碱抑制活性测试显示，与丁酰胆碱酯酶（BuChE）相比，大部分化合物显示出对乙酰胆碱酯酶（AChE）的高选择性和良好的抑制活性.其中活性最好的化合物（2-氨基-4-（3-氰基苯基）-5，10-二氧代-5，10-二氢-4H-苯并[g]亚甲基-3-甲腈）（3n），其AChE抑制活性IC₅₀值为1.22 μmol/L，比BuChE高164倍.此外，分子对接模拟研究为理解这些化合物的作用机制、效力及选择性提供了理论支持.这些新型有效且高度选择性的AChE抑制剂的发现为开发阿尔茨海默症的潜在治疗药物提供了先导化合物.
关键词: 吡喃并[2,3-b]萘醌, 乙酰胆碱酯酶抑制剂, 阿尔兹海默症, 分子模拟
A novel synthetic methodology was developed and a series of pyrano[2,3-b]naphthoquinone derivatives were designed and synthesized in excellent yields. Most of these compounds showed effective anti-AChE activities and high selectivity for acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Among them, (2-Amino-4-(3-cyanophenyl)-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene-3-carbonitrile) (3n) was significantly potent, with an IC₅₀ value of 1.22 μmol/L for AChE, which was 164-fold higher than butyrylcholinesterase (BuChE) in vitro. Moreover, molecular modeling provides valuable information for understanding the potency and selectivity of this kind of compounds for AChE. Consequently, these potent and highly selective AChE inhibitors are potential leads for development of the drug for treatment of Alzheimer's disease.
Key words: pyrano[2,3-b]naphthoquinone, acetylcholinesterase (AChE) inhibitor, Alzheimer's disease, molecular modeling


PDF全文下载地址:

点我下载PDF