阿魏酸衍生物的合成及其抗胆碱酯酶活性
Synthesis of ferulic acid derivatives and their inhibition of cholinesterase inhibitory activity
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摘要: 阿魏酸（ferulic acid，FA）是一种含酚羟基的苯丙素类天然产物，药理活性广泛，对于阿尔茨海默病（Alzheimer′s disease，AD）具有一定疗效。以FA为原料，通过甲酯化对羧基进行保护，拼接氨基甲酸酯活性官能团，水解反应以及酰胺缩合等4步反应首次合成一系列阿魏酸氨基甲酸酯苯胺衍生物，采用Ellman法对FA衍生物进行体外抑制胆碱酯酶活性评价。共设计合成15个新颖的FA衍生物，结构经1H NMR、13C NMR、ESI-MS 确证；体外胆碱酯酶活性测试显示，化合物5c，5f，5j，5g，5m 5个化合物对乙酰胆碱酯酶具有抑制作用，除化合物5l，5m以外，几乎所有化合物都对丁酰胆碱酯酶具有抑制活性，且远高于乙酰胆碱酯酶抑制活性。化合物5c，5f，5j，5g可以作为潜在的靶向胆碱酯酶的AD治疗药物。Abstract: Ferulic acid (FA), a natural product of phenylpropanoids containing phenolic hydroxyl groups, has a wide range of pharmacological activities and some therapeutic effect on Alzheimer's disease (AD).Using FA as the raw material, the ferulic acid carbamate aniline derivatives were first synthesized by 4-step esterification reaction, splicing carbamate active functional groups, hydrolysis reaction and amide condensation.These FA derivatives were evaluated for in vitro cholinesterase inhibition activity by the Ellman method.A total of 15 novel FA derivatives were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR and ESI-MS.Cholinesterase activity tests showed that compounds 5c, 5f, 5j, 5g, 5m possessed good acetylcholinesterase inhibition activity.Except for 5l, 5m, almost all compounds have inhibition activity on butyrylcholinesterase, which is much higher than that on acetylcholinesterase.In conclusion, compounds 5c, 5f, 5j and 5g can be used as potential anti-AD inhibitors targeting cholinesterase..
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Keywords:
- ferulic acid /
- derivatives /
- synthesis /
- Alzheimer's disease /
- cholinesterase inhibitor /
- Ellman method
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