New 3-amino-2-thioxothiazolidin-4-one-based inhibitors of acetyl- and butyryl-cholinesterase: synthesis and activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F24%3A10488020" target="_blank" >RIV/00216208:11160/24:10488020 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=fsiJjMoE8" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=fsiJjMoE8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4155/fmc-2023-0268" target="_blank" >10.4155/fmc-2023-0268</a>

Jazyk výsledku

angličtina

Název v původním jazyce

New 3-amino-2-thioxothiazolidin-4-one-based inhibitors of acetyl- and butyryl-cholinesterase: synthesis and activity

Popis výsledku v původním jazyce

Aim: 2-Thioxothiazolidin-4-one represents a versatile scaffold in drug development. The authors used it to prepare new potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors that can be utilized, e.g., to treat Alzheimer&apos;s disease. Materials &amp; methods: 3-Amino-2-thioxothiazolidin-4-one was modified at the amino group or active methylene, using substituted benzaldehydes. The derivatives were evaluated for inhibition of AChE and BChE (Ellman&apos;s method). Results &amp; conclusion: The derivatives were obtained with yields of 52-94%. They showed dual inhibition with IC50 values from 13.15 mu M; many compounds were superior to rivastigmine. The structure-activity relationship favors nitrobenzylidene and 3,5-dihalogenosalicylidene scaffolds. AChE was inhibited noncompetitively, whereas BChE was inhibited with a mixed type of inhibition. Molecular docking provided insights into molecular interactions. Each enzyme is inhibited by a different binding mode.

Název v anglickém jazyce

New 3-amino-2-thioxothiazolidin-4-one-based inhibitors of acetyl- and butyryl-cholinesterase: synthesis and activity

Popis výsledku anglicky

Aim: 2-Thioxothiazolidin-4-one represents a versatile scaffold in drug development. The authors used it to prepare new potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors that can be utilized, e.g., to treat Alzheimer&apos;s disease. Materials &amp; methods: 3-Amino-2-thioxothiazolidin-4-one was modified at the amino group or active methylene, using substituted benzaldehydes. The derivatives were evaluated for inhibition of AChE and BChE (Ellman&apos;s method). Results &amp; conclusion: The derivatives were obtained with yields of 52-94%. They showed dual inhibition with IC50 values from 13.15 mu M; many compounds were superior to rivastigmine. The structure-activity relationship favors nitrobenzylidene and 3,5-dihalogenosalicylidene scaffolds. AChE was inhibited noncompetitively, whereas BChE was inhibited with a mixed type of inhibition. Molecular docking provided insights into molecular interactions. Each enzyme is inhibited by a different binding mode.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Future Medicinal Chemistry

ISSN

1756-8919

e-ISSN

1756-8927

Svazek periodika

16

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

59-74

Kód UT WoS článku

001112538400001

EID výsledku v databázi Scopus

2-s2.0-85182597816