This work evaluated the in vitro effect of thiazolidin-4-ones on the activity of AChE (total and isoforms) isolated from the cerebral cortex, hippocampus, and lymphocytes. Kinetic parameters were evaluated and molecular docking was performed. Our results showed that thiazolidinones derived from 4-(methylthio)benzaldehyde (1) and from 4-(methylsulfonyl)benzaldehyde (2) were capable of inhibiting the AChE activity in vitro. Three compounds, two with a propylpiperidine (1b and 2b) moiety and one with a 3-(diethylamino)propyl (1c) moiety showed IC50 values of 13.81 μM, and 3.13 μM (1b), 55.36 μM and 44.33 μM (1c) for cerebral cortex and hippocampus, respectively, and 3.11 μM for both (2b). Enzyme kinetics revealed that the type of AChE inhibition was mixed. Compound 1b inhibited the G1 and G4 AChE isoforms, while compounds 1c and 2b selectively inhibited the G4 isoform. Molecular docking showed a possible three-dimensional fit into the enzyme. Our findings showed that these thiazolidin-4-ones, especially those containing the propylpiperidine core, have a potential cholinesterase inhibitory activity and can be considered good candidates for future Alzheimer's therapy.

中文翻译：

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2- {4- [甲硫基（甲基磺酰基）]苯基} -3-取代的噻唑烷酮-4-酮对大鼠脑和淋巴细胞乙酰胆碱酯酶活性的体外影响：同工型选择性，动力学分析和分子对接。

这项工作评估了噻唑烷丁4酮对从大脑皮层，海马和淋巴细胞分离的AChE（总和同工型）活性的体外作用。评估动力学参数并进行分子对接。我们的结果表明，源自4-（甲硫基）苯甲醛（1）和源自4-（甲磺酰基）苯甲醛（2）的噻唑烷酮能够在体外抑制AChE活性。三种化合物（两种具有丙基哌啶（1b和2b）部分，一种具有3-（二乙氨基）丙基（1c）部分）的IC50值分别为13.81μM和3.13μM（1b），55.36μM和44.33μM（1c）。分别为大脑皮层和海马，两者均为3.11μM（2b）。酶动力学表明，AChE抑制的类型是混合的。化合物1b抑制了G1和G4 AChE亚型，而化合物1c和2b选择性抑制G4亚型。分子对接表明该酶可能在三维上适合。我们的研究结果表明，这些噻唑烷酮-4-酮，特别是那些含有丙基哌啶核心的噻唑烷酮-4-酮，具有潜在的胆碱酯酶抑制活性，可以被视为未来阿尔茨海默氏症治疗的良好候选者。