Laboratory of Research in Medicinal Chemistry (PeQuiM), Federal University of Alfenas, Jovino Fernandes Sales Avenue, 2600, Alfenas, MG 37130000, Brazil.
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
Molecules. 2020 Jul 10;25(14):3165. doi: 10.3390/molecules25143165.
(AD) is a neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ oligomers in neuronal SH-SY5Y cells. In parallel, compound showed a good profile of safety and ADME parameters. Taken together, these results suggest that could be considered a lead compound for the further development of AD therapeutics.
（AD）是一种神经退行性疾病，涉及不同的发病机制。在这方面，本研究的目的是通过将姜黄素和白藜芦醇的结构片段通过酰腙功能连接到 1,4-二取代三唑系统来设计和合成具有多功能药理活性的新化合物。在这些杂合化合物中，衍生物 表现出抑制乙酰胆碱酯酶活性、细胞内活性氧形成以及 Aβ 低聚物在神经元 SH-SY5Y 细胞中引起的神经毒性的能力。同时，化合物 表现出良好的安全性和 ADME 参数特征。综上所述，这些结果表明 可以被认为是进一步开发 AD 治疗药物的先导化合物。
