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Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies

One of the symptoms of Alzheimer’s disease (AD) is low acetylcholine level due to high acetylcholinesterase (AChE) activity. For this reason, AChE inhibitors are used in the treatment of AD, the prolonged use of which may cause a cholinergic crisis. There is a need to search for safe natural AChE in...

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Autores principales: Budryn, Grażyna, Majak, Iwona, Grzelczyk, Joanna, Szwajgier, Dominik, Rodríguez-Martínez, Alejandro, Pérez-Sánchez, Horacio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227119/
https://www.ncbi.nlm.nih.gov/pubmed/35745206
http://dx.doi.org/10.3390/nu14122476
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author Budryn, Grażyna
Majak, Iwona
Grzelczyk, Joanna
Szwajgier, Dominik
Rodríguez-Martínez, Alejandro
Pérez-Sánchez, Horacio
author_facet Budryn, Grażyna
Majak, Iwona
Grzelczyk, Joanna
Szwajgier, Dominik
Rodríguez-Martínez, Alejandro
Pérez-Sánchez, Horacio
author_sort Budryn, Grażyna
collection PubMed
description One of the symptoms of Alzheimer’s disease (AD) is low acetylcholine level due to high acetylcholinesterase (AChE) activity. For this reason, AChE inhibitors are used in the treatment of AD, the prolonged use of which may cause a cholinergic crisis. There is a need to search for safe natural AChE inhibitors. The study analyzed 16 hydroxybenzoic acids using calorimetry and docking simulation as AChE inhibitors. All tested compounds were shown to inhibit the hydrolysis of ACh. The best properties were shown by methyl syringinate, which acted as competitive inhibitor at a catalytic site. The tested compounds also interacted with the anionic or peripheral binding site known to block β-amyloid plaques formation. The activity of the tested hydroxybenzoic acids IC50 ranged from 5.50 to 34.19 µmol/µmol of AChE, and the binding constant Ka from 20.53 to 253.16 L/mol, which proves their reversible, non-toxic effect, and activity at physiological concentrations.
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spelling pubmed-92271192022-06-25 Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies Budryn, Grażyna Majak, Iwona Grzelczyk, Joanna Szwajgier, Dominik Rodríguez-Martínez, Alejandro Pérez-Sánchez, Horacio Nutrients Article One of the symptoms of Alzheimer’s disease (AD) is low acetylcholine level due to high acetylcholinesterase (AChE) activity. For this reason, AChE inhibitors are used in the treatment of AD, the prolonged use of which may cause a cholinergic crisis. There is a need to search for safe natural AChE inhibitors. The study analyzed 16 hydroxybenzoic acids using calorimetry and docking simulation as AChE inhibitors. All tested compounds were shown to inhibit the hydrolysis of ACh. The best properties were shown by methyl syringinate, which acted as competitive inhibitor at a catalytic site. The tested compounds also interacted with the anionic or peripheral binding site known to block β-amyloid plaques formation. The activity of the tested hydroxybenzoic acids IC50 ranged from 5.50 to 34.19 µmol/µmol of AChE, and the binding constant Ka from 20.53 to 253.16 L/mol, which proves their reversible, non-toxic effect, and activity at physiological concentrations. MDPI 2022-06-15 /pmc/articles/PMC9227119/ /pubmed/35745206 http://dx.doi.org/10.3390/nu14122476 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Budryn, Grażyna
Majak, Iwona
Grzelczyk, Joanna
Szwajgier, Dominik
Rodríguez-Martínez, Alejandro
Pérez-Sánchez, Horacio
Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies
title Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies
title_full Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies
title_fullStr Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies
title_full_unstemmed Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies
title_short Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies
title_sort hydroxybenzoic acids as acetylcholinesterase inhibitors: calorimetric and docking simulation studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227119/
https://www.ncbi.nlm.nih.gov/pubmed/35745206
http://dx.doi.org/10.3390/nu14122476
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