Effects of novel 17 beta-hydroxysteroid dehydrogenase type 10 inhibitors on mitochondrial respiration

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10422751" target="_blank" >RIV/00216208:11110/21:10422751 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62690094:18470/21:50017837 RIV/00179906:_____/21:10422751 RIV/00064165:_____/21:10422751

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.toxlet.2020.12.012" target="_blank" >10.1016/j.toxlet.2020.12.012</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effects of novel 17 beta-hydroxysteroid dehydrogenase type 10 inhibitors on mitochondrial respiration

Popis výsledku v původním jazyce

Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer&apos;s disease (AD). The enzyme 17 beta-hydroxysteroid dehydrogenase type 10 (HSD10) is a multifunctional mitochondrial protein that is thought to play a role in the pathophysiology of AD and is one of the targets of new potential AD drugs. The in vitro effects of frentizole, riluzole, AG18051, and 42 novel modulators of HSD10 (potential AD drugs) on citrate synthase (CS) activity, monoamine oxidase (MAO) activity, complex I- or complex II-linked mitochondrial respiratory rate, and complex I activity were measured in isolated pig brain mitochondria. Based on their minimal inhibitory effects on the respiratory rate of mitochondria and CS and complex I activity, six novel compounds were selected for further testing. Assuming that inhibition of MAO-B could be a desirable effect of AD drugs, only AG18051 and one new compound met the criteria for MAO-B inhibition with minimal drug-induced effects on mitochondrial respiration. In conclusion, our in vitro screening of mitochondrial effect of novel potential AD drugs has enabled the selection of the most promising molecules for further testing that are relatively safe in terms of drug-induced mitochondrial toxicity. (C) 2020 Elsevier B.V. All rights reserved.

Název v anglickém jazyce

Effects of novel 17 beta-hydroxysteroid dehydrogenase type 10 inhibitors on mitochondrial respiration

Popis výsledku anglicky

Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer&apos;s disease (AD). The enzyme 17 beta-hydroxysteroid dehydrogenase type 10 (HSD10) is a multifunctional mitochondrial protein that is thought to play a role in the pathophysiology of AD and is one of the targets of new potential AD drugs. The in vitro effects of frentizole, riluzole, AG18051, and 42 novel modulators of HSD10 (potential AD drugs) on citrate synthase (CS) activity, monoamine oxidase (MAO) activity, complex I- or complex II-linked mitochondrial respiratory rate, and complex I activity were measured in isolated pig brain mitochondria. Based on their minimal inhibitory effects on the respiratory rate of mitochondria and CS and complex I activity, six novel compounds were selected for further testing. Assuming that inhibition of MAO-B could be a desirable effect of AD drugs, only AG18051 and one new compound met the criteria for MAO-B inhibition with minimal drug-induced effects on mitochondrial respiration. In conclusion, our in vitro screening of mitochondrial effect of novel potential AD drugs has enabled the selection of the most promising molecules for further testing that are relatively safe in terms of drug-induced mitochondrial toxicity. (C) 2020 Elsevier B.V. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30215 - Psychiatry

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)

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Toxicology Letters

ISSN

0378-4274

e-ISSN

—

Svazek periodika

339

Číslo periodika v rámci svazku

March

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

8

Strana od-do

12-19

Kód UT WoS článku

000608184700002

EID výsledku v databázi Scopus

2-s2.0-85098687901