A series of multitarget ligands was designed by introducing several structurally diverse aminoacetamide groups at position 6 of the deoxyvasicinone group, with the aim of obtaining novel multifunctional anti-Alzheimer's disease agents using deoxyvasicinone as the substrate. In vitro studies showed that almost all of the derivatives were potent inhibitors of human recombinant acetylcholinesterase (hAChE) and human serum butyrylcholinesterase (hBChE), with IC₅₀ values in the low nanomolar range, and exhibited moderate to high inhibition of Aβ₁₋₄₂ self-aggregation. In particular, compounds 12h, 12n, and 12q showed promising inhibitory activity for hAChE, with IC₅₀ values of 5.31 ± 2.8, 4.09 ± 0.23, and 7.61 ± 0.53 nM, respectively. Compounds 12h and 12q also exhibited the greatest ability to inhibit hBChE, with IC₅₀ values of 4.35 ± 0.32 and 2.35 ± 0.14 nM, respectively. Moreover, enzyme kinetics confirmed that compound 12q caused a mixed type of AChE inhibition, by binding to both the active sites (PAS and CAS) of AChE. Remarkably, compound 12q also demonstrated the highest potential inhibitory activity for Aβ₁₋₄₂ self-aggregation (63.9 ± 4.9%, 10 μM), and it was also an excellent metal chelator.

通过在脱氧维辛酮基团的6位引入几个结构上不同的氨基乙酰胺基团，设计了一系列多靶配体，目的是使用脱氧维辛酮作为底物获得新型的多功能抗阿尔茨海默氏病药物。体外研究显示，几乎所有的衍生物是人重组乙酰胆碱酯酶（的有效抑制剂ħ乙酰胆碱酯酶）和人血清丁酰胆碱酯酶（ħ的BChE）中，用IC _50点在低纳摩尔范围内的值，并表现出中度至高度抑制A的β _{1 −42}自聚集。特别是化合物12h，12n和12q对h AChE具有抑制作用，IC ₅₀值分别为5.31±2.8、4.09±0.23和7.61±0.53 nM。化合物12h和12q也表现出最大的抑制h BChE的能力，IC ₅₀值分别为4.35±0.32和2.35±0.14 nM。此外，酶动力学证实化合物12q通过与AChE的两个活性位点（PAS和CAS）结合而引起了混合型的AChE抑制。值得注意的是，化合物12Q还展示了A中的最高电位的抑制活性β _1-42 自聚集（63.9±4.9％，10μM），它也是一种出色的金属螯合剂。