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Discovery of novel dual acetylcholinesterase inhibitors with antifibrillogenic activity related to Alzheimer's disease.
Future Med Chem. 2018 05 01; 10(9):1037-1053.FM

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

de Almeida JR
Departamento de Ciências Farmacêuticas, Universidade de São Paulo, Av. do Café, s/n - Ribeirão Preto - SP, CEP 14040-903, Brazil.
Figueiro M
Institute of Chemistry, University of Campinas, 13083-970, Campinas-SP, Brazil.
Almeida WP
Faculty of Pharmaceutical Sciences and Institute of Chemistry, University of Campinas, 13081-970, Campinas-SP, Brazil.
de Paula da Silva CHT
Departamento de Ciências Farmacêuticas, Universidade de São Paulo, Av. do Café, s/n - Ribeirão Preto - SP, CEP 14040-903, Brazil.

MeSH

AcetylcholinesteraseAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCholinesterase InhibitorsDrug DesignElectrophorusHumansMolecular Docking SimulationProtein Aggregates

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29676170

Citation

de Almeida, Jonathan R., et al. "Discovery of Novel Dual Acetylcholinesterase Inhibitors With Antifibrillogenic Activity Related to Alzheimer's Disease." Future Medicinal Chemistry, vol. 10, no. 9, 2018, pp. 1037-1053.
de Almeida JR, Figueiro M, Almeida WP, et al. Discovery of novel dual acetylcholinesterase inhibitors with antifibrillogenic activity related to Alzheimer's disease. Future Med Chem. 2018;10(9):1037-1053.
de Almeida, J. R., Figueiro, M., Almeida, W. P., & de Paula da Silva, C. H. T. (2018). Discovery of novel dual acetylcholinesterase inhibitors with antifibrillogenic activity related to Alzheimer's disease. Future Medicinal Chemistry, 10(9), 1037-1053. https://doi.org/10.4155/fmc-2017-0201
de Almeida JR, et al. Discovery of Novel Dual Acetylcholinesterase Inhibitors With Antifibrillogenic Activity Related to Alzheimer's Disease. Future Med Chem. 2018 05 1;10(9):1037-1053. PubMed PMID: 29676170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovery of novel dual acetylcholinesterase inhibitors with antifibrillogenic activity related to Alzheimer's disease. AU - de Almeida,Jonathan R, AU - Figueiro,Micheli, AU - Almeida,Wanda Pereira, AU - de Paula da Silva,Carlos Henrique Tomich, Y1 - 2018/04/20/ PY - 2018/4/21/pubmed PY - 2019/2/5/medline PY - 2018/4/21/entrez KW - Alzheimer's disease KW - antifibrillogenic activity KW - multitarget SP - 1037 EP - 1053 JF - Future medicinal chemistry JO - Future Med Chem VL - 10 IS - 9 N2 - 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. SN - 1756-8927 UR - https://www.unboundmedicine.com/medline/citation/29676170/Discovery_of_novel_dual_acetylcholinesterase_inhibitors_with_antifibrillogenic_activity_related_to_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -