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  • Title: Discovery of novel dual acetylcholinesterase inhibitors with antifibrillogenic activity related to Alzheimer's disease.
    Author: de Almeida JR, Figueiro M, Almeida WP, de Paula da Silva CHT.
    Journal: Future Med Chem; 2018 May 01; 10(9):1037-1053. PubMed ID: 29676170.
    Abstract:
    AIM: Alzheimer's disease is a progressive and neurodegenerative disorder of the CNS, affecting elderly people. The current pharmacological approach is based on the improvement of cholinergic neurotransmission by inhibiting acetylcholinesterase (AChE) with AChE inhibitors. The disease is also characterized by the accelerated accumulation of β-amyloid plaques around neurons. Furthermore, in vitro studies revealed that AChE can induce β-amyloid peptide (Aβ) aggregation. METHODOLOGY: Computer-aided molecular design by virtual screening was here employed to discover novel potential AChE inhibitors, with antifibrillogenic properties, in other words, inhibiting Aβ aggregation. RESULTS: Compounds 1, 4 and 6 showed interesting AChE inhibition. In addition, they particularly inhibit Aβ aggregation in vitro, indicating to be promising novel anti-Alzheimer agents.
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