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J Enzyme Inhib Med Chem. 2019 Dec;34(1):429-437. doi: 10.1080/14756366.2018.1543288.

Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies.

Author information

1
a Department of Mathematics and Science Education, Education Faculty , Dumlupınar University , Kutahya , Turkey.
2
b Department of Basic Sciences of Pharmacy, Pharmacy Faculty , Agri Ibrahim Cecen University , Agri , Turkey.
3
c Department of Chemistry , Science and Art Faculty, Agri Ibrahim Cecen University , Agri , Turkey.
4
d Department of Biophysics, Computational Biology and Molecular Simulations Laboratory , Bahcesehir University, School of Medicine , Istanbul , Turkey.
5
e Department of Neurofarba , University of Florence , Sesto Fiorentino (Firenze) , Italy.
6
f Department of Agricultural Biotechnology , Agriculture Faculty, Ondokuz Mayis University , Samsun , Turkey.

Abstract

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) inhibitors are interesting compounds for different therapeutic applications, among which Alzheimer's disease. Here, we investigated the inhibition of these cholinesterases with uracil derivatives. The mechanism of inhibition of these enzymes was observed to be due to obstruction of the active site entrance by the inhibitors scaffold. Molecular docking and molecular dynamics (MD) simulations demonstrated the possible key interactions between the studied ligands and amino acid residues at different regions of the active sites of AChE and BuChE. Being diverse of the classical AChE and BuChE inhibitors, the investigated uracil derivatives may be used as lead molecules for designing new therapeutically effective enzyme inhibitors.

KEYWORDS:

Alzheimer’s disease; MD simulations; acetylcholinesterase; butyrylcholinesterase; docking; inhibitor; uracil derivatives

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