Sym-Triazines for directed multitarget modulation of cholinesterases and amyloid-β in Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is a complex neurodegenerative disorder marked by numerous causative factors of disease progression, termed pathologies. We report here the synthesis of a small library of novel sym-triazine compounds designed for targeted modulation of multiple pathologies related to AD, specifically human acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and Aβ aggregation. Rational targeting of AChE was achieved by the incorporation of acetylcholine substrate analogues into a sym-triazine core in either a mono-, di-, or trisubstituted regime. A subset of these derivatives demonstrated improved activity compared to several commercially available cholinesterase inhibitors. High AChE/BuChE selectivity was characteristic of all derivatives, and AChE steady-state kinetics i

SUBMITTER: Veloso AJ 

PROVIDER: S-EPMC3582285 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature