Synthesis and neuroprotective activity of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F23%3A00578898" target="_blank" >RIV/61389030:_____/23:00578898 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216275:25310/23:39920494 RIV/00098892:_____/23:10158392 RIV/61989592:15310/23:73620295 RIV/61989592:15110/23:73620295

Výsledek na webu

<a href="https://doi.org/10.1002/ardp.202300378" target="_blank" >https://doi.org/10.1002/ardp.202300378</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ardp.202300378" target="_blank" >10.1002/ardp.202300378</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and neuroprotective activity of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives

Popis výsledku v původním jazyce

A library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives was prepared from N-Boc-3-azetidinone employing the Horner-Wadsworth-Emmons reaction, rhodium(I)-catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N-unprotected hydrochlorides, N-alkylated and N-acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol-induced) and aspects of Alzheimer's disease (glutamate-induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol- and glutamate-induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase-3/7 activity.

Název v anglickém jazyce

Synthesis and neuroprotective activity of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives

Popis výsledku anglicky

A library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives was prepared from N-Boc-3-azetidinone employing the Horner-Wadsworth-Emmons reaction, rhodium(I)-catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N-unprotected hydrochlorides, N-alkylated and N-acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol-induced) and aspects of Alzheimer's disease (glutamate-induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol- and glutamate-induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase-3/7 activity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

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

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

Archiv der Pharmazie

ISSN

0365-6233

e-ISSN

1521-4184

Svazek periodika

356

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

19

Strana od-do

2300378

Kód UT WoS článku

001078968900001

EID výsledku v databázi Scopus

2-s2.0-85173483202