Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents

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 IC50 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.