席夫碱衍生物的合成及其抗阿尔茨海默病活性研究

Synthesis and biological evaluation of Schiff base derivatives for the treatment of alzheimer's disease

目的设计、合成了2个席夫碱衍生物,并测试其生物活性。方法通过熔点、~1H NMR和^(13)C NMR进行结构确证;分别采用硫黄素T法与透射电子显微镜法测定目标化合物抑制Aβ1-42自身聚集活性,采用氧自由基吸收能力法测定抗氧化活性,采用MTT法测定神经保护作用,以及采用紫外-可见分光光度法测定金属离子络合能力。结果目标化合物双水杨醛缩水合肼席夫碱(T1)和双水杨醛缩乙二胺席夫碱(T2)结构经确证,其中化合物T2具有较强的抑制Aβ1-42自身聚集活性(抵制率达42.8%)和选择性金属离子络合能力,同时拥有良好的抗氧化活性及神经保护作用。结论化合物T2是一个潜在多靶点抗阿尔茨海默病药物,具有良好的开发前景。

Objective To synthesize two Schiff base derivatives and evaluate the inhibition of self-induced Aβ1-42,antioxidant,and metal chelating potency.Methods The structure of target compounds was characterized by1H NMR,13C NMR and melting point.The biological activities were evaluated by Thioflavin T,TEM,ORAC and MTT assay.Results The results showed that the synthesized compounds had potent inhibition towards self-induced Aβ1-42,antioxidant and chelating ability.Among of the compounds,compound T2indicated significant inhibitory potency towards self-induced Aβ1-42with42.8%inhibition ratio,good antioxidant activity and neuroprotective effect,as well as a selective metal chelating agent.Conclusion The compound T2could serve as a drug-seed in developing anti-alzheimer's agents.