N-substituted arylhydroxamic acids as acetylcholinesterase reactivators

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F23%3A00558348" target="_blank" >RIV/60162694:G44__/23:00558348 - isvavai.cz</a>

Alternative codes found

RIV/62690094:18470/22:50019338 RIV/00179906:_____/22:10449527

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0009279722002836?pes=vor" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0009279722002836?pes=vor</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cbi.2022.110078" target="_blank" >10.1016/j.cbi.2022.110078</a>

Result language

angličtina

Original language name

N-substituted arylhydroxamic acids as acetylcholinesterase reactivators

Original language description

The problem of the efficient treatment of acute organophosphorus (OP) poisoning needs more efforts in the development of a versatile antidote, applicable for treatment of the injuries of both peripheral and central nervous systems. A series of N-H, N-methyl, N-butyl, and N-phenyl derivatives of benzhydroxamic (1a-1d), 3-methoxybenzhydroxamic (2a-2d), 4-methoxybenzhydroxamic (3a-3d) acids, and corresponding salycilhydroxamates (4a-4d) was prepared. Their predicted hydrophobicity (log P) was evaluated as regards to ??? score by the open access cheminformatics tools; prediction of the passive transport across the BBB was found by means on the parallel artificial membrane permeability assay (PAMPA). The data on reactivation capacity of human acetylcholinesterase (HssAChE) inhibited by GB, VX, and paraoxon was supported by molecular docking study on binding to the active site of the AChE, viability study against mammalian cells (Chinese hamster ovary CHO-K1), and biodegradability (Closed Bottle test OECD 301D). Among the studied compounds, N-butyl derivatives have better balanced combination of properties; among them, N-butylsalicylhydroxamic acid is most promising. The studied compounds demonstrate modest reactivation capacity; change of N-H by N-Me ensures the reactivation capacity in studied concentrations on all studied OP substrates; among N-butyl derivatives, the N-butylsalicylhydroxamic acid demonstrates most promising results within the series. The found regularities may lead to selection of perspective structures to complement current formulations for medical countermeasures against poisoning by organophosphorus toxicants.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA22-12859S" target="_blank" >GA22-12859S: Novichok nerve agents - toxicity and countermeasures</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2022

Confidentiality

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

Name of the periodical

Chemico-Biological Interactions

ISSN

0009-2797

e-ISSN

1872-7786

Volume of the periodical

365

Issue of the periodical within the volume

Sep

Country of publishing house

IE - IRELAND

Number of pages

13

Pages from-to

110078

UT code for WoS article

000860712100002

EID of the result in the Scopus database

2-s2.0-85135787878