Design, synthesis, and evaluation of genipin derivatives for the treatment of Alzheimer's Disease

: Twenty-two novel genipin derivatives have been designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE). As a result, compound 13a bearing ligustrazine moiety displayed the most potent AChE inhibitory activity in this series with IC50 value of 218 nm. Besides, MTT assay was performed to investigate the neuroprotection of these compounds against PC12 cells injured by Amyloid β-protein 1-42 (Aβ1-42 ). Among them, 8a showed higher inhibition rate (%Inhibition = 22.29) than the positive reference Donepezil (%Inhibition = 17.65).