A series of genistein-polyamine conjugates(4a–4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases(Ch Es) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase(ACh E) with an IC_(50) value of 2.75 μmol/L, which was better than that of rivastigmine(5.60 μmol/L). Lineweaver–Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site(CAS) and the peripheral anionic site(PAS) of ACh E. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a–4h did not affect Hep G-2 cell viability at the concentration of 10 μmol/L.
