Benzothiazolyl Ureas are Low Micromolar and Uncompetitive Inhibitors of 17 beta-HSD10 with Implications to Alzheimer's Disease Treatment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50016755" target="_blank" >RIV/62690094:18470/20:50016755 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/20:00555807

Výsledek na webu

<a href="https://www.mdpi.com/1422-0067/21/6/2059" target="_blank" >https://www.mdpi.com/1422-0067/21/6/2059</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21062059" target="_blank" >10.3390/ijms21062059</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Benzothiazolyl Ureas are Low Micromolar and Uncompetitive Inhibitors of 17 beta-HSD10 with Implications to Alzheimer's Disease Treatment

Popis výsledku v původním jazyce

Human 17 beta-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson&apos;s disease, or Alzheimer&apos;s disease, in which it was shown to interact with the amyloid-beta peptide. We prepared approximately 60 new compounds based on a benzothiazolyl scaffold and evaluated their inhibitory ability and mechanism of action. The most potent inhibitors contained 3-chloro and 4-hydroxy substitution on the phenyl ring moiety, a small substituent at position 6 on the benzothiazole moiety, and the two moieties were connected via a urea linker (4at, 4bb, and 4bg). These compounds exhibited IC50 values of 1-2 mu M and showed an uncompetitive mechanism of action with respect to the substrate, acetoacetyl-CoA. These uncompetitive benzothiazolyl inhibitors of 17 beta-hydroxysteroid dehydrogenase type 10 are promising compounds for potential drugs for neurodegenerative diseases that warrant further research and development.

Název v anglickém jazyce

Benzothiazolyl Ureas are Low Micromolar and Uncompetitive Inhibitors of 17 beta-HSD10 with Implications to Alzheimer's Disease Treatment

Popis výsledku anglicky

Human 17 beta-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson&apos;s disease, or Alzheimer&apos;s disease, in which it was shown to interact with the amyloid-beta peptide. We prepared approximately 60 new compounds based on a benzothiazolyl scaffold and evaluated their inhibitory ability and mechanism of action. The most potent inhibitors contained 3-chloro and 4-hydroxy substitution on the phenyl ring moiety, a small substituent at position 6 on the benzothiazole moiety, and the two moieties were connected via a urea linker (4at, 4bb, and 4bg). These compounds exhibited IC50 values of 1-2 mu M and showed an uncompetitive mechanism of action with respect to the substrate, acetoacetyl-CoA. These uncompetitive benzothiazolyl inhibitors of 17 beta-hydroxysteroid dehydrogenase type 10 are promising compounds for potential drugs for neurodegenerative diseases that warrant further research and development.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

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

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

International journal of molecular sciences

ISSN

1661-6596

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

26

Strana od-do

"Article Number: 2059"

Kód UT WoS článku

000529890200155

EID výsledku v databázi Scopus

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