前胡内酯肟酯衍生物的合成及其抑制乙酰胆碱酯酶活性评价

Synthesis and Biological Evaluation of Imperatorin-based Oxime Esters as Acetylcholinesterase Inhibitor

本文以香豆素类化合物前胡内酯为先导化合物,设计合成了12个前胡内酯肟酯衍生物,所有目标化合物经熔点、1H NMR和MS进行结构确证。体外抑制乙酰胆碱酯酶(AChE)活性评价结果表明,在1μmol/mL浓度下,目标化合物4a和4k对AChE具有较强的抑制活性,其抑制率分别达到58.05%和66.27%。初步构效关系研究表明,引入吲哚环能提高前胡内酯对AChE的抑制活性。通过分子对接方法考察了化合物4k与AChE结合的模式,发现目标化合物可以和AChE的催化活性中心部位结合。

Twelve imperatorin-based oxime ester derivatives were synthesized and their structures were confirmed by melting point, 1H NMR and MS. Preliminary bioassay result of these derivatives′ activities inhibiting acetylcholinesterase(AChE) in vivo showed that compounds 4 a and 4 k had potential inhibitory activities with 66.27% and 58.05%, respectively. The preliminary study on the structure-activity relationships indicated that introduction of indole could enhance the activity. Molecular docking study suggested that 4 k possessed an optimal docking pose with interactions inside AChE.