Chen_2018_Int.J.Biol.Macromol_107_2725

A series of 4- substituted sampangine derivatives (4-aminoalkylaminosampangine Ar-NH(CH2)nNR1R2) has been designed, synthesized, and tested for their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and beta-myloid (Abeta) aggregation. The synthetic compounds exhibited high AChE inhibitory activity and a significant in vitro inhibitory potency toward the self-induced Abeta aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human beta-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Abeta42 secretion levels. Moreover, most of the synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. The result encourages us to study this class of compounds thoroughly and systematically.