In this work, a new series of aryl(4-phenylpiperazin-1-yl)methanethione derivatives 4a-n was designed, synthesized, and evaluated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. Most of the synthesized derivatives were more potent than standard inhibitor donepezil against AChE and all the synthesized compounds were more potent than donepezil against BChE. Moreover, some of these new compounds were more potent than acarbose (positive control) against α-glucosidase. The obtained results revealed that (3-chlorophenyl)(4-phenylpiperazin-1-yl)methanethione 4k and was the most potent compound against cholinesterase enzymes (AChE and BChE). Docking study of compound 4k in the active site of cholinesterase enzymes showed that this compound established important interactions with the main residues of the target enzymes. Druglikeness/ADME/Toxicity profile prediction of the most potent compounds also demonstrated that these compounds can be drug candidates and have the appropriate properties in terms of ADME and Toxicity.

在这项工作中，设计、合成了一系列新的芳基（4-苯基哌嗪-1-基）甲硫酮衍生物4a-n，并针对乙酰胆碱酯酶 (AChE)、丁酰胆碱酯酶 (BChE) 和 α-葡萄糖苷酶进行了评估。大多数合成的衍生物比标准抑制剂多奈哌齐对 AChE 更有效，所有合成的化合物都比多奈哌齐对 BChE 更有效。此外，其中一些新化合物比阿卡波糖（阳性对照）对 α-葡萄糖苷酶更有效。获得的结果表明，(3-氯苯基)(4-苯基哌嗪-1-基)甲硫酮4k是对胆碱酯酶 (AChE 和 BChE) 最有效的化合物。复合4k对接研究在胆碱酯酶的活性位点表明该化合物与靶酶的主要残基建立了重要的相互作用。对最有效化合物的药物相似性/ADME/毒性谱预测也表明，这些化合物可以是候选药物，并且在 ADME 和毒性方面具有适当的特性。