2-Hydroxy-N-phenylbenzamides and Their Esters Inhibit Acetylcholinesterase and Butyrylcholinesterase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F19%3A10400967" target="_blank" >RIV/00216208:11160/19:10400967 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216275:25310/19:39915565

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FWbdPAaKFu" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FWbdPAaKFu</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biom9110698" target="_blank" >10.3390/biom9110698</a>

Jazyk výsledku

angličtina

Název v původním jazyce

2-Hydroxy-N-phenylbenzamides and Their Esters Inhibit Acetylcholinesterase and Butyrylcholinesterase

Popis výsledku v původním jazyce

The development of novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) represents a viable approach to alleviate Alzheimer&apos;s disease. Thirty-six halogenated 2-hydroxy-N-phenylbenzamides (salicylanilides) with various substitution patterns and their esters with phosphorus-based acids were synthesized in yields of 72% to 92% and characterized. They were evaluated for in vitro inhibition of AChE from electric eel and BuChE from equine serum using modified Ellman&apos;s spectrophotometric method. The benzamides exhibited a moderate inhibition of AChE with IC50 values in a narrow concentration range from 33.1 to 85.8 mu M. IC50 values for BuChE were higher (53.5-228.4 mu M). The majority of derivatives inhibit AChE more efficiently than BuChE and are comparable or superior to rivastigmine-an established cholinesterases inhibitor used in the treatment of Alzheimer&apos;s disease. Phosphorus-based esters especially improved the activity against BuChE with 5-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl diethyl phosphite 5c superiority (IC50 = 2.4 mu M). This derivative was also the most selective inhibitor of BuChE. It caused a mixed inhibition of both cholinesterases and acted as a pseudo-irreversible inhibitor. Several structure-activity relationships were identified, e.g., favouring esters and benzamides obtained from 5-halogenosalicylic acids and polyhalogenated anilines. Both 2-hydroxy-N-phenylbenzamides and esters share convenient physicochemical properties for blood-brain-barrier penetration and thus central nervous system delivery.

Název v anglickém jazyce

2-Hydroxy-N-phenylbenzamides and Their Esters Inhibit Acetylcholinesterase and Butyrylcholinesterase

Popis výsledku anglicky

The development of novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) represents a viable approach to alleviate Alzheimer&apos;s disease. Thirty-six halogenated 2-hydroxy-N-phenylbenzamides (salicylanilides) with various substitution patterns and their esters with phosphorus-based acids were synthesized in yields of 72% to 92% and characterized. They were evaluated for in vitro inhibition of AChE from electric eel and BuChE from equine serum using modified Ellman&apos;s spectrophotometric method. The benzamides exhibited a moderate inhibition of AChE with IC50 values in a narrow concentration range from 33.1 to 85.8 mu M. IC50 values for BuChE were higher (53.5-228.4 mu M). The majority of derivatives inhibit AChE more efficiently than BuChE and are comparable or superior to rivastigmine-an established cholinesterases inhibitor used in the treatment of Alzheimer&apos;s disease. Phosphorus-based esters especially improved the activity against BuChE with 5-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl diethyl phosphite 5c superiority (IC50 = 2.4 mu M). This derivative was also the most selective inhibitor of BuChE. It caused a mixed inhibition of both cholinesterases and acted as a pseudo-irreversible inhibitor. Several structure-activity relationships were identified, e.g., favouring esters and benzamides obtained from 5-halogenosalicylic acids and polyhalogenated anilines. Both 2-hydroxy-N-phenylbenzamides and esters share convenient physicochemical properties for blood-brain-barrier penetration and thus central nervous system delivery.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Biomolecules

ISSN

2218-273X

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

16

Strana od-do

698

Kód UT WoS článku

000502267900059

EID výsledku v databázi Scopus

2-s2.0-85074624860