Inhibition of amyloid fibrillization of amyloid β peptide by 4,7-disubsti-tuted coumarin derivatives

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10500993" target="_blank" >RIV/00179906:_____/25:10500993 - isvavai.cz</a>

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2025.118302" target="_blank" >10.1016/j.bmc.2025.118302</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Inhibition of amyloid fibrillization of amyloid β peptide by 4,7-disubsti-tuted coumarin derivatives

Popis výsledku v původním jazyce

Coumarins are well-known for their unique chemical structure and a wide range of biological effects. Various substituted coumarin-based compounds have emerged as promising candidates for the development of novel therapeutic agents against numerous diseases. This study was focused on the synthesis of new 4,7-disubstituted coumarin derivatives and investigation of their ability to inhibit the aggregation of Aβ40 peptide, their cytotoxic effect on SH-SY5Y cells, their antioxidant properties, and their ability to penetrate the blood-brain barrier (BBB). The results revealed that the trihydroxy derivatives 5a-c had been the most effective inhibitors of Aβ aggregation, promoting the formation of non-toxic, amorphous aggregates instead. Importantly, no significant decrease in the viability of SH-SY5Y neuroblastoma cells was observed after treatment with the studied coumarins. Among them, coumarin 5a demonstrated the strongest antioxidant activity, while compound 5b also exhibited good antioxidant properties, along with the best inhibition of Aβ aggregation (IC50 = 13.5 μM), and adequate permeability across the blood-brain barrier. These findings suggest that compound 5b is a promising candidate for further investigation in Alzheimer&apos;s disease pharmacotherapy.

Název v anglickém jazyce

Inhibition of amyloid fibrillization of amyloid β peptide by 4,7-disubsti-tuted coumarin derivatives

Popis výsledku anglicky

Coumarins are well-known for their unique chemical structure and a wide range of biological effects. Various substituted coumarin-based compounds have emerged as promising candidates for the development of novel therapeutic agents against numerous diseases. This study was focused on the synthesis of new 4,7-disubstituted coumarin derivatives and investigation of their ability to inhibit the aggregation of Aβ40 peptide, their cytotoxic effect on SH-SY5Y cells, their antioxidant properties, and their ability to penetrate the blood-brain barrier (BBB). The results revealed that the trihydroxy derivatives 5a-c had been the most effective inhibitors of Aβ aggregation, promoting the formation of non-toxic, amorphous aggregates instead. Importantly, no significant decrease in the viability of SH-SY5Y neuroblastoma cells was observed after treatment with the studied coumarins. Among them, coumarin 5a demonstrated the strongest antioxidant activity, while compound 5b also exhibited good antioxidant properties, along with the best inhibition of Aβ aggregation (IC50 = 13.5 μM), and adequate permeability across the blood-brain barrier. These findings suggest that compound 5b is a promising candidate for further investigation in Alzheimer&apos;s disease pharmacotherapy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Bioorganic &amp; Medicinal Chemistry

ISSN

0968-0896

e-ISSN

1464-3391

Svazek periodika

129

Číslo periodika v rámci svazku

NOV

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

118302

Kód UT WoS článku

001548063600001

EID výsledku v databázi Scopus

2-s2.0-105010931547