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Molecules 2018, 23(8), 2033; https://doi.org/10.3390/molecules23082033

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

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Aden University, 6075 Aden, Yemen
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
3
Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
4
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
*
Author to whom correspondence should be addressed.
Academic Editor: Praveen P. Nekkar Rao
Received: 29 July 2018 / Revised: 10 August 2018 / Accepted: 12 August 2018 / Published: 14 August 2018
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Abstract

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. View Full-Text
Keywords: Alzheimer’s disease; acetylcholinesterase; butyrylcholinesterase; 9-aminoacridine; dithiocarbamate salts; docking study Alzheimer’s disease; acetylcholinesterase; butyrylcholinesterase; 9-aminoacridine; dithiocarbamate salts; docking study
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Hussein, W.; Sağlık, B.N.; Levent, S.; Korkut, B.; Ilgın, S.; Özkay, Y.; Kaplancıklı, Z.A. Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer’s Disease. Molecules 2018, 23, 2033.

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