Liao_2015_Bioorg.Med.Chem.Lett_25_1541

A series of 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that the target compounds exhibited good acetylcholinesterase (AChE) inhibitory potencies, high selectivity toward AChE over butyrylcholinesterase (BCHE), potential antioxidant activities and significant inhibitory potencies of self-induced beta-amyloid peptide (Abeta) aggregation. In particular, compound 14c had the strongest AChE inhibitory activity with IC50 value of 12.8nM, potent inhibition of self-induced Abeta1-42 aggregation with inhibition ratio of 33.8% at 25muM. Moreover, compound 14c acted as an antioxidant, as well as a neuroprotectant. Furthermore, 14c could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 14c might be a potential multifunctional candidate for the treatment of AD.