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Twenty-four genistein-O-1,3,5-triazine derivatives were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. These compounds were confirmed by IR, NMR and HRMS and single-crystal X-ray diffraction studies. Most target compounds showed good inhibition and selectivity to acetylcholinesterase. Among these compounds, compound 4 e (7-((4-chloro-6-(diisobutylamino)-1,3,5-triazin-2-yl)oxy)-5hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) exhibited the strongest inhibition to acetylcholinesterase with IC 50 of 0.034 μM, which was comparable with that of donepezil (IC 50 = 0.037 μM). The enzyme kinetics studies showed that this compound was a kind of mixed type inhibitor. Molecular docking and molecular dynamics simulations study of this compound indicated that it could interact with the crucial amino acids present at the catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and bind to acetylcholinesterase stably. Furthermore, this compound also showed terrific metal chelating abilities. ADMET characteristics implied that these compounds could possess the properties to become drug candidates. Thus, this compound may become a latent multifunctional anti-Alzheimer agent.