Abstractí¬Natural ()-huperzine B (HupB), isolated from Chinese medicinal herb, displayed moderate inhibitory activity of acetylcholinesterase
(AChE). Based on the active dual-site of AChE, a series of novel derivatives of bis- and bifunctional HupB were
designed and synthesized. The AChE inhibition potency of most derivatives of HupB was enhanced about 2ĘC3 orders of magnitude
as compared with the parental HupB. Among bis-HupB derivatives, 12h exhibited the most potent in the AChE inhibition and has
been evaluated for its pharmacological actions in vivo on ChE inhibition, cognitive enhancement, and neuroprotection. The docking
study on the bis-HupB derivatives 12 series with TcAChE has demonstrated that the ligands bound to the dual-site of the enzyme in
different level.