氧化异阿朴菲-褪黑素杂合体的合成、抗β淀粉样蛋白聚集及抗氧化活性

Synthesis,Inhibition of β-Amyloid Aggregation and Antioxidation of Oxoisoaporphine-Melatonin Hybrids

基于多靶向策略设计合成了氧化异阿朴菲-褪黑素杂合化合物,测试了它们的抗胆碱酯酶性能及相应的抑制动力学、抗氧化能力和抑制乙酰胆碱酯酶诱导的β-淀粉样蛋白(Aβ)聚集能力。实验结果表明,所合成的化合物对乙酰胆碱酯酶具有中等强度抑制力,其抑制IC50值在微摩尔浓度水平,属于非竞争性抑制剂;对乙酰胆碱酯酶诱导的Aβ淀粉样蛋白聚集的抑制率达到79.3%～84.7%;抗氧化能力是trolox的1.1～1.5倍。

Two oxoisoaporphine-melatonin hybrids（compound 2a and 2b） have been designed,synthesized and tested for their ability to inhibit acetylcholinesterase,butyrylcholinesterase,acetylcholinesterase-induced β-amyloid（Aβ） aggregation.Their inhibitory mechanism and antioxidant properties were also studied.The synthetic compounds（2a and 2b） exhibited moderate AChE inhibitory activity with IC50 values in the micromolar range in most cases.Non-competitive binding mode was found for these derivatives.Moreover,the compounds（2a and 2b） exhibit high acetylcholinesterase-induced Aβ antiaggregating activity with inhibitory potencies ranging from 79.3% to 84.7%,and significant antioxidant properties with peroxyl radical absorbance capacities ranging from 1.1-to 1.5-fold the value of trolox.