Sulaiman Bin Abdullah Aba Al-Khail-Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS), International Islamic University 44000 Islamabad, Pakistan.
School of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
Bioorg Chem. 2019 Mar;84:518-528. doi: 10.1016/j.bioorg.2018.12.002. Epub 2018 Dec 5.
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 IC value of 0.0023 ± 0.0002 μM, 88-folds stronger inhibition than standard drug (neostigmine methyl sulphate; IC = 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.
一种高效的一锅四组分策略涉及醛、胺、炔烃和异硫氰酸酯，用于合成一系列新型噻唑烷-2-亚胺（5a-x）。该过程在由 Cu(I) 和 Zn(II) 组成的协同催化作用下进行，以良好至优异的收率得到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形成的亚胺或炔丙胺，并通过原位形成的炔丙基硫脲的分子内 5-endo-dig 氢硫代反应进行。此外，这些基序的生物应用通过其对乙酰胆碱酯酶（AChE）的强烈抑制活性得到证明，其中化合物 5s 被鉴定为具有 AChE 抑制活性的先导化合物，IC 值为 0.0023 ± 0.0002 μM，比标准药物（新斯的明甲硫酸盐；IC = 0.203 ± 0.004 μM）强 88 倍。分子对接分析证实了体外生物活性结果，表明该有效先导化合物与酶活性位点中的氨基酸残基形成了几种有用的相互作用。
