An efficient one-pot four-component strategy involving aldehydes, amines, alkynes and isothiocyanates has been developed to access a novel series of thiazolidine-2-imines (5a-x). This process operates under the action of a cooperative catalysis composed of Cu(I) and Zn(II) delivering the desired five-membered heterocyclic compounds in good to excellent yields. Notably, this transformation avoids the use of pre-formed imines or propargylamines and proceeds via an intramolecular 5-exo-dig hydrothiolation reaction of the in situ formed propargyl thiourea. Furthermore, the biological application of these motifs was demonstrated in terms of their strong acetylcholinesterase (AChE) inhibitory activity where compound 5s was identified as the lead AChE inhibitor with an IC50 value of 0.0023 ± 0.0002 μM, 88-folds stronger inhibition than standard drug (neostigmine methyl sulphate; IC50 = 0.203 ± 0.004 μM). Molecular docking analysis reinforced the in vitro biological activity results revealing the formation of several useful interactions of the potent lead with amino acid residues in the active site of the enzyme.

中文翻译：

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使用CuI / ZnII双​​重催化一锅四组分合成噻唑烷-2-亚胺：一类新的乙酰胆碱酯酶抑制剂。

已经开发出一种有效的一锅四组分策略，该策略涉及醛，胺，炔烃和异硫氰酸酯，以开发一系列新颖的噻唑烷-2-亚胺（5a-x）。该方法在由Cu（I）和Zn（II）组成的协同催化作用下进行，以良好至极佳的产率提供所需的五元杂环化合物。值得注意的是，这种转化避免了使用预先形成的亚胺或炔丙基胺，而是通过原位形成的炔丙基硫脲的分子内5-外切氢加氢氧化反应进行的。此外，这些基序的生物学应用还表现出强大的乙酰胆碱酯酶（AChE）抑制活性，其中化合物5s被鉴定为主要的AChE抑制剂，IC50值为0.0023±0.0002μM，抑制作用比标准药物（新斯的明甲基硫酸盐； IC50 = 0.203±0.004μM）强88倍。分子对接分析增强了体外生物活性结果，揭示了有效的先导分子与酶活性位点中氨基酸残基的几种有用相互作用的形成。