Background: Acetylcholine deficiency in the hippocampus and cortex, aggregation of amyloid-beta, and beta-secretase overactivity have been introduced as the main reasons in the formation of Alzheimer’s disease.

Objective: A new series of cinnamic derived acids linked to 1-benzyl-1,2,3-triazole moiety were designed, synthesized, and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities.

Methods: Colorimetric Ellman’s method was used for the determination of IC50% of AchE and BuChE inhibitory activity. The kinetic studies, neuroprotective activity, BACE1 inhibitory activity, evaluation of inhibitory potency on Aβ1-42 self-aggregation induced by AchE, and docking study were performed for studying the mechanism of action.

Results: Some of the synthesized compounds, compound 7b-4 ((E)-3-(3,4-dimethoxyphenyl)-N-((1- (4-fluorobenzyl)-1H-1,2,3-triazole-4-yl) methyl) acrylamide) depicted the most potent acetylcholinesterase inhibitory activities ( IC50 = 5.27 μM ) and compound 7a-1 (N- ( (1- benzyl- 1H- 1, 2, 3- triazole - 4-yl) methyl) cinnamamide) demonstrated the most potent butyrylcholinesterase inhibitory activities (IC50 = 1.75 μM). Compound 7b-4 showed neuroprotective and β-secretase (BACE1) inhibitory activitiy. In vivo studies of compound 7b-4 in Scopolamine-induced dysfunction confirmed memory improvement.

Conclusion: It should be noted that molecular modeling (compounds 7b-4 and 7a-1) and kinetic studies (compounds 7a-1 and 7b-4) showed that these synthesis compounds interacted simultaneously with both the catalytic site (CS) and peripheral anionic site (PAS) of AChE and BuChE.

背景：海马和皮质的乙酰胆碱缺乏症，淀粉样β蛋白的聚集和β-分泌酶过度活跃已被引入，这是阿尔茨海默氏病形成的主要原因。

目的：设计，合成和链接到一系列新的肉桂酸衍生的1-苄基-1,2,3-三唑部分的乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制活性。

方法：采用比色Ellman法测定AchE的IC50％和BuChE的抑制活性。进行了动力学研究，神经保护活性，BACE1抑制活性，对AchE诱导的Aβ1-42自聚集的抑制能力评价以及对接研究以研究其作用机理。

结果：一些合成的化合物，化合物7b-4（（E）-3-（3,4-二甲氧基苯基）-N-（（1-（4-氟苄基）-1H-1,2,3-三唑-4 -yl）甲基）丙烯酰胺）表现出最强的乙酰胆碱酯酶抑制活性（IC50 = 5.27μM）和化合物7a-1（N-（（1-苄基-1H-1、2、3-三唑-4-基）甲基）肉桂酰胺）表现出最强的丁酰胆碱酯酶抑制活性（IC50 = 1.75μM）。化合物7b-4显示出神经保护和β-分泌酶（BACE1）抑制活性。Scopolamine诱导的功能障碍的化合物7b-4的体内研究证实了记忆力的改善。

结论：应注意的是，分子建模（化合物7b-4和7a-1）和动力学研究（化合物7a-1和7b-4）表明，这些合成化合物同时与催化位点（CS）和外围阴离子相互作用AChE和BuChE的网站（PAS）。