A series of berberine-thiophenyl hybrids were designed, synthesised, and evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and β-amyloid (Aβ) aggregation and as antioxidants. Among these hybrids, compounds 4f and 4i, berberine linked with o-methylthiophenyl and o-chlorothiophenyl by a 2-carbon spacer, were observed to be potent inhibitors of AChE, with IC50 values of 0.077 and 0.042 μM, respectively. Of the tested compounds, 4i was also the most potent inhibitor of BuChE, with an IC50 value of 0.662 μM. Kinetic studies and molecular modelling simulations of the AChE-inhibitor complex indicated that a mixed-competitive binding mode existed for these berberine derivatives. The biological studies also demonstrated that these hybrids displayed interesting activities, including Aβ aggregation inhibition and antioxidant properties.

译文

设计,合成和评估了一系列小檗碱-噻吩杂化物,作为乙酰胆碱酯酶 (AChE),丁酰胆碱酯酶 (BuChE) 和 β-淀粉样蛋白 (A β) 聚集的抑制剂和抗氧化剂。在这些杂化物中,观察到化合物4f和4i,通过2-碳间隔物与o-甲基噻吩和o-氯噻吩连接的小檗碱是AChE的有效抑制剂,IC50值分别为0.077和0.042。在测试的化合物中,4i也是最有效的BuChE抑制剂,IC50值为0.662微米。AChE抑制剂复合物的动力学研究和分子建模模拟表明,这些小檗碱衍生物存在混合竞争结合模式。生物学研究还表明,这些杂种表现出有趣的活性,包括a β 聚集抑制和抗氧化特性。

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