Discovery of novel dual acetylcholinesterase inhibitors with antifibrillogenic activity related to Alzheimer's disease

• Published in: Future medicinal chemistry Vol. 10; no. 9; pp. 1037 - 1053
• Main Authors: de Almeida, Jonathan R, Figueiro, Micheli, Almeida, Wanda Pereira, de Paula da Silva, Carlos Henrique Tomich
• Format: Journal Article
• Language: English
• Published: England Future Science Ltd 01.05.2018
• Subjects: Acetylcholinesterase - metabolism; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - metabolism; Animals; antifibrillogenic activity; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Drug Design; Electrophorus; Humans; Molecular Docking Simulation; multitarget; Protein Aggregates - drug effects; Alzheimer's disease; multitarget; antifibrillogenic activity
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2017-0201

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, studies revealed that AChE can induce β-amyloid peptide (Aβ) aggregation. 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. Compounds and showed interesting AChE inhibition. In addition, they particularly inhibit Aβ aggregation , indicating to be promising novel anti-Alzheimer agents.