Novel Benzothiazole-Based Ureas as 17 beta-HSD10 Inhibitors, A Potential Alzheimer's Disease Treatment
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F19%3A50015709" target="_blank" >RIV/62690094:18470/19:50015709 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00179906:_____/19:10398712
Výsledek na webu
<a href="https://www.mdpi.com/1420-3049/24/15/2757" target="_blank" >https://www.mdpi.com/1420-3049/24/15/2757</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/molecules24152757" target="_blank" >10.3390/molecules24152757</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Novel Benzothiazole-Based Ureas as 17 beta-HSD10 Inhibitors, A Potential Alzheimer's Disease Treatment
Popis výsledku v původním jazyce
It has long been established that mitochondrial dysfunction in Alzheimer's disease (AD) patients can trigger pathological changes in cell metabolism by altering metabolic enzymes such as the mitochondrial 17 beta-hydroxysteroid dehydrogenase type 10 (17 beta-HSD10), also known as amyloid-binding alcohol dehydrogenase (ABAD). We and others have shown that frentizole and riluzole derivatives can inhibit 17 beta-HSD10 and that this inhibition is beneficial and holds therapeutic merit for the treatment of AD. Here we evaluate several novel series based on benzothiazolylurea scaffold evaluating key structural and activity relationships required for the inhibition of 17 beta-HSD10. Results show that the most promising of these compounds have markedly increased potency on our previously published inhibitors, with the most promising exhibiting advantageous features like low cytotoxicity and target engagement in living cells.
Název v anglickém jazyce
Novel Benzothiazole-Based Ureas as 17 beta-HSD10 Inhibitors, A Potential Alzheimer's Disease Treatment
Popis výsledku anglicky
It has long been established that mitochondrial dysfunction in Alzheimer's disease (AD) patients can trigger pathological changes in cell metabolism by altering metabolic enzymes such as the mitochondrial 17 beta-hydroxysteroid dehydrogenase type 10 (17 beta-HSD10), also known as amyloid-binding alcohol dehydrogenase (ABAD). We and others have shown that frentizole and riluzole derivatives can inhibit 17 beta-HSD10 and that this inhibition is beneficial and holds therapeutic merit for the treatment of AD. Here we evaluate several novel series based on benzothiazolylurea scaffold evaluating key structural and activity relationships required for the inhibition of 17 beta-HSD10. Results show that the most promising of these compounds have markedly increased potency on our previously published inhibitors, with the most promising exhibiting advantageous features like low cytotoxicity and target engagement in living cells.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30107 - Medicinal chemistry
Návaznosti výsledku
Projekt
<a href="/cs/project/EF18_069%2F0010054" target="_blank" >EF18_069/0010054: IT4Neuro(degeneration)</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2019
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Molecules
ISSN
1420-3049
e-ISSN
—
Svazek periodika
24
Číslo periodika v rámci svazku
15
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
23
Strana od-do
"Article Number: 2757"
Kód UT WoS článku
000482441100080
EID výsledku v databázi Scopus
—