Arylboronic acids as safe and specific human butyrylcholinesterase inhibitors

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

Arylboronic acids as safe and specific human butyrylcholinesterase inhibitors

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

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

Name of the periodical

Journal of molecular structure

ISSN

0022-2860

e-ISSN

1872-8014

Volume of the periodical

1290

Issue of the periodical within the volume

October

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

14

Pages from-to

"Article number: 135932"

UT code for WoS article

001027586600001

EID of the result in the Scopus database

2-s2.0-85162163051