Abstract：
A completely green protocol was developed for the synthesis of a series of arylaminonaphthol derivatives in the presence of N-ethylethanolamine (NEEA) as a catalyst under ultrasonic irradiation and solventless conditions. The major assets of this methodology were the use of non-toxic organic medium, available catalyst, mild reaction condition, and good to excellent yield of desired products. All of the synthesized products were screened for their in vitro antioxidant activity using DPPH, ABTS, and Ferric-phenanthroline assays and it was found that most of them are potent antioxidant agents. Also, their butyrylcholinesterase inhibitory activity has been investigated in vitro. All tested compounds exhibited potential inhibitory activity toward BuChE when compared to standard reference drug galantamine, however, compounds 4r, 4u, 4 g and 4x gave higher butyrylcholinesterase inhibitory with IC50 values of 14.78 ± 0.65 µM, 16.18 ± 0.50 µM, 20.00 ± 0.50 µM, and 20.28 ± 0.08 µM respectively. On the other hand, we employed density functional theory (DFT), calculations to analyze molecular geometry and global reactivity descriptors, and MESP analysis to predict electrophilic and nucleophilic attacks. A quantitative structure-activity relationship (QSAR) investigation was conducted on the antioxidant and butyrylcholinesterase properties of 25 arylaminonaphthol derivatives, resulting in robust and satisfactory models. To evaluate their anti-Alzheimer\'s activity, compounds 4 g, 4q, 4r, 4u, and 4x underwent docking simulations at the active site of the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), revealing why these compounds displayed superior activity, consistent with the biological findings.
摘要：
开发了一种完全绿色的方案，用于在超声辐照和无溶剂条件下，在N-乙基乙醇胺（NEEA）作为催化剂的存在下合成一系列芳基氨基萘酚衍生物。这种方法的主要资产是使用无毒的有机介质，可用的催化剂，温和的反应条件，以及所需产品的良好至优异收率。使用DPPH筛选了所有合成产物的体外抗氧化活性，ABTS,和铁-菲咯啉测定，发现它们中的大多数是有效的抗氧化剂。此外，它们的丁酰胆碱酯酶抑制活性已在体外进行了研究。与标准参考药物加兰他敏相比，所有测试化合物均对BuChE表现出潜在的抑制活性，然而,化合物4r,4u,4g和4x产生更高的丁酰胆碱酯酶抑制作用，IC50值为14.78±0.65µM，16.18±0.50µM,20.00±0.50µM,和20.28±0.08µM。另一方面,我们采用密度泛函理论(DFT)，分析分子几何形状和全局反应性描述符的计算，和MESP分析来预测亲电和亲核攻击。对25个芳氨基萘酚衍生物的抗氧化和丁酰胆碱酯酶特性进行了定量构效关系（QSAR）研究，产生稳健和令人满意的模型。为了评估他们的抗阿尔茨海默氏症活性，化合物4g,4q,4r,4u,并在乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的活性位点进行了4x对接模拟，揭示了为什么这些化合物表现出优异的活性，与生物学结果一致。
