Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder mostly influencing the elderly, and causes death due to dementia. The main pathogenic feature connected with the progression of this multifactorial disease is the weakening of the cholinergic system in the brain. Cholinesterase (ChE) inhibitor...

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Autores principales: Hussein, Weiam, Sağlık, Begüm Nurpelin, Levent, Serkan, Korkut, Büşra, Ilgın, Sinem, Özkay, Yusuf, Kaplancıklı, Zafer Asım
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222329/
https://www.ncbi.nlm.nih.gov/pubmed/30110946
http://dx.doi.org/10.3390/molecules23082033
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author Hussein, Weiam
Sağlık, Begüm Nurpelin
Levent, Serkan
Korkut, Büşra
Ilgın, Sinem
Özkay, Yusuf
Kaplancıklı, Zafer Asım
author_facet Hussein, Weiam
Sağlık, Begüm Nurpelin
Levent, Serkan
Korkut, Büşra
Ilgın, Sinem
Özkay, Yusuf
Kaplancıklı, Zafer Asım
author_sort Hussein, Weiam
collection PubMed
description Alzheimer’s disease (AD) is a neurodegenerative disorder mostly influencing the elderly, and causes death due to dementia. The main pathogenic feature connected with the progression of this multifactorial disease is the weakening of the cholinergic system in the brain. Cholinesterase (ChE) inhibitors are recognized as one of the choices in the treatment of AD. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were approved as a therapeutic strategy to reduce the symptoms of AD and prevent its progression. The capacity of BChE is not completely known yet; rather, it is accepted to assume a part in a few disorders such as AD. Thus, BChE inhibitors may have a greater role for the treatment of AD in the future. In the present study, 2-(9-acridinylamino)-2-oxoethyl piperazine/piperidine/morpholinecarbodithioate derivatives were synthesized in order to investigate anticholinesterase activity. Eight derivatives demonstrated a specific and promising action against BChE. Furthermore, compound 4n showed inhibitory activity against both enzymes. It was found that the active compounds were well tolerated in the cytotoxicity test. Possible interactions between the lead compound, 4n, and the BChE enzyme were determined through a docking study. The findings obtained within this paper will contribute to the development of new and effective synthetic anti-Alzheimer compounds, and will ideally encourage future screening against AD.
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spelling pubmed-62223292018-11-13 Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease Hussein, Weiam Sağlık, Begüm Nurpelin Levent, Serkan Korkut, Büşra Ilgın, Sinem Özkay, Yusuf Kaplancıklı, Zafer Asım Molecules Article Alzheimer’s disease (AD) is a neurodegenerative disorder mostly influencing the elderly, and causes death due to dementia. The main pathogenic feature connected with the progression of this multifactorial disease is the weakening of the cholinergic system in the brain. Cholinesterase (ChE) inhibitors are recognized as one of the choices in the treatment of AD. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were approved as a therapeutic strategy to reduce the symptoms of AD and prevent its progression. The capacity of BChE is not completely known yet; rather, it is accepted to assume a part in a few disorders such as AD. Thus, BChE inhibitors may have a greater role for the treatment of AD in the future. In the present study, 2-(9-acridinylamino)-2-oxoethyl piperazine/piperidine/morpholinecarbodithioate derivatives were synthesized in order to investigate anticholinesterase activity. Eight derivatives demonstrated a specific and promising action against BChE. Furthermore, compound 4n showed inhibitory activity against both enzymes. It was found that the active compounds were well tolerated in the cytotoxicity test. Possible interactions between the lead compound, 4n, and the BChE enzyme were determined through a docking study. The findings obtained within this paper will contribute to the development of new and effective synthetic anti-Alzheimer compounds, and will ideally encourage future screening against AD. MDPI 2018-08-14 /pmc/articles/PMC6222329/ /pubmed/30110946 http://dx.doi.org/10.3390/molecules23082033 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hussein, Weiam
Sağlık, Begüm Nurpelin
Levent, Serkan
Korkut, Büşra
Ilgın, Sinem
Özkay, Yusuf
Kaplancıklı, Zafer Asım
Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease
title Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease
title_full Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease
title_fullStr Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease
title_full_unstemmed Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease
title_short Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease
title_sort synthesis and biological evaluation of new cholinesterase inhibitors for alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222329/
https://www.ncbi.nlm.nih.gov/pubmed/30110946
http://dx.doi.org/10.3390/molecules23082033
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