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

Abstract

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 (Aβ_1-42 ). Among them, 8a showed higher inhibition rate (%Inhibition = 22.29) than the positive reference Donepezil (%Inhibition = 17.65).