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4- Substituted sampangine derivatives: Novel acetylcholinesterase and β-myloid aggregation inhibitors.
International Journal of Biological Macromolecules 2018 Februrary
A series of 4- substituted sampangine derivatives (4-aminoalkylaminosampangine Ar-NH(CH2 )n NR1 R2 ) has been designed, synthesized, and tested for their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-myloid (Aβ) aggregation. The synthetic compounds exhibited high AChE inhibitory activity and a significant in vitro inhibitory potency toward the self-induced Aβ aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Aβ42 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.
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