Arylboronic acids as safe and specific human butyrylcholinesterase inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50020485" target="_blank" >RIV/62690094:18470/23:50020485 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0022286023010268?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0022286023010268?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molstruc.2023.135932" target="_blank" >10.1016/j.molstruc.2023.135932</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Arylboronic acids as safe and specific human butyrylcholinesterase inhibitors

Popis výsledku v původním jazyce

The drug treatment of Alzheimer&apos;s disease (AD) remains a significant scientific challenge, necessitating a continual search for new drug candidates. In this context, we present here, for the first time, new oxime-arylboronic acid hybrids (L1-L6) as potential anti-AD agents. These hybrids were synthesized and evaluated for their inhibitory capabilities on the activity of non-human cholinesterases [Electrophorus electricus Acetylcholinesterase (EeAChE) and Equine Butyrylcholinesterase (EqBChE)] as well as human cholinesterases [erythrocyte Acetylcholinesterase (hAChE) and plasma Butyrylcholinesterase (hBChE)]. We also assessed the safety of these compounds in a microglia cell line and analyzed the compound-enzyme interactions using molecular docking and molecular dynamics simulations. All compounds were found to be safe for the tests conducted. None of them exhibited significant inhibitory activity against hAChE or EeAChE. However, L1-L5 demonstrated inhibition of EqBChE and hBChE, with L3 being the most potent inhibitor of hBChE (IC50 = 6.41 ± 0.62 µM) and EqBChE (IC50 = 81.28 ± 4.01 µM). Additionally, L2, L3, and L5 showed 8–15 times higher potency as inhibitors of hBChE compared to EqBChE. These findings indicate that the hybrid oxime-arylboronic acids act as specific inhibitors of BChE, with a notable selectivity for hBChE, making them promising structures for the development of more potent and selective hBChE inhibitors. © 2023 Elsevier B.V.

Název v anglickém jazyce

Arylboronic acids as safe and specific human butyrylcholinesterase inhibitors

Popis výsledku anglicky

The drug treatment of Alzheimer&apos;s disease (AD) remains a significant scientific challenge, necessitating a continual search for new drug candidates. In this context, we present here, for the first time, new oxime-arylboronic acid hybrids (L1-L6) as potential anti-AD agents. These hybrids were synthesized and evaluated for their inhibitory capabilities on the activity of non-human cholinesterases [Electrophorus electricus Acetylcholinesterase (EeAChE) and Equine Butyrylcholinesterase (EqBChE)] as well as human cholinesterases [erythrocyte Acetylcholinesterase (hAChE) and plasma Butyrylcholinesterase (hBChE)]. We also assessed the safety of these compounds in a microglia cell line and analyzed the compound-enzyme interactions using molecular docking and molecular dynamics simulations. All compounds were found to be safe for the tests conducted. None of them exhibited significant inhibitory activity against hAChE or EeAChE. However, L1-L5 demonstrated inhibition of EqBChE and hBChE, with L3 being the most potent inhibitor of hBChE (IC50 = 6.41 ± 0.62 µM) and EqBChE (IC50 = 81.28 ± 4.01 µM). Additionally, L2, L3, and L5 showed 8–15 times higher potency as inhibitors of hBChE compared to EqBChE. These findings indicate that the hybrid oxime-arylboronic acids act as specific inhibitors of BChE, with a notable selectivity for hBChE, making them promising structures for the development of more potent and selective hBChE inhibitors. © 2023 Elsevier B.V.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of molecular structure

ISSN

0022-2860

e-ISSN

1872-8014

Svazek periodika

1290

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

14

Strana od-do

"Article number: 135932"

Kód UT WoS článku

001027586600001

EID výsledku v databázi Scopus

2-s2.0-85162163051