Abstract

Five 1,4-bisphenylhydrazone derivatives (1–5) were successfully synthesized and evaluated for their antioxidant and acetylcholinesterase inhibitory activities. The antioxidant activity has been carried out using DPPH, ABTS, CUPRAC and superoxide radical scavenging methods. All the compounds showed a very good antioxidant activity compared to that of the standards used. Compound 1 was found to be the best antioxidant agent with IC₅₀ values lower or comparable to that of the standards. The acetylcholinesterase inhibitory activity has been evaluated using a modified Ellman’s assay. The obtained results indicate that compound 2 is the best acetylcholinesterase inhibitor with a low IC₅₀ value comparable to that of the galantamine. In addition, DFT calculations have been performed to determine in which mechanism the synthesized hydrazones follow to scavenge free radicals. Molecular docking study was performed for compound 2, and its interaction modes with the enzyme acetylcholinesterase were determined. As a result, a strong interaction between this compound and the active site of AChE enzyme was revealed. Finally, ADME properties of the synthesized compounds were also studied and showed good drug-like properties.

Graphic abstract

摘要

成功合成了五种 1,4-双苯腙衍生物 ( 1 – 5 ) 并评估了它们的抗氧化和乙酰胆碱酯酶抑制活性。已使用 DPPH、ABTS、CUPRAC 和超氧自由基清除方法进行抗氧化活性。与使用的标准品相比，所有化合物都显示出非常好的抗氧化活性。发现化合物1是最好的抗氧化剂，其IC ₅₀值低于或与标准品相当。乙酰胆碱酯酶抑制活性已使用改良的 Ellman 测定法进行评估。所得结果表明化合物2是最好的乙酰胆碱酯酶抑制剂，IC ₅₀较低值与加兰他敏相当。此外，还进行了 DFT 计算以确定合成腙清除自由基的机制。对化合物2进行了分子对接研究，确定了其与乙酰胆碱酯酶的相互作用模式。结果，揭示了该化合物与 AChE 酶的活性位点之间的强烈相互作用。最后，还研究了合成化合物的 ADME 特性，并显示出良好的类药物特性。

图形摘要