• Je něco špatně v tomto záznamu ?

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

Z. Fišar, K. Musílek, O. Benek, L. Hroch, L. Vinklářová, M. Schmidt, J. Hroudová, J. Raboch

. 2021 ; 339 (-) : 12-19. [pub] 20201224

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc21011429

Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). The enzyme 17β-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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21011429
003      
CZ-PrNML
005      
20221025122958.0
007      
ta
008      
210420s2021 ne f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.toxlet.2020.12.012 $2 doi
035    __
$a (PubMed)33359020
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Fišar, Zdeněk $u Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Psychiatry, Ke Karlovu 11, 120 00, Prague 2, Czech Republic. Electronic address: zfisar@lf1.cuni.cz
245    10
$a Effects of novel 17β-hydroxysteroid dehydrogenase type 10 inhibitors on mitochondrial respiration / $c Z. Fišar, K. Musílek, O. Benek, L. Hroch, L. Vinklářová, M. Schmidt, J. Hroudová, J. Raboch
520    9_
$a Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). The enzyme 17β-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.
650    _2
$a 17-hydroxysteroidní dehydrogenasy $x antagonisté a inhibitory $x toxicita $7 D015067
650    _2
$a zvířata $7 D000818
650    _2
$a buněčné dýchání $x účinky léků $7 D019069
650    _2
$a inhibitory enzymů $x terapeutické užití $x toxicita $7 D004791
650    _2
$a lidé $7 D006801
650    _2
$a mitochondrie $x účinky léků $7 D008928
650    _2
$a modely u zvířat $7 D023421
650    _2
$a neurodegenerativní nemoci $x farmakoterapie $7 D019636
650    _2
$a prasata $7 D013552
655    _2
$a časopisecké články $7 D016428
700    1_
$a Musílek, Kamil $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic. Electronic address: kamil.musilek@gmail.com
700    1_
$a Benek, Ondřej $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic
700    1_
$a Hroch, Lukáš $u University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic
700    1_
$a Vinklářová, Lucie $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic
700    1_
$a Schmidt, Monika $u University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic $7 xx0278043
700    1_
$a Hroudová, Jana $u Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Psychiatry, Ke Karlovu 11, 120 00, Prague 2, Czech Republic
700    1_
$a Raboch, Jiří $u Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Psychiatry, Ke Karlovu 11, 120 00, Prague 2, Czech Republic
773    0_
$w MED00004537 $t Toxicology letters $x 1879-3169 $g Roč. 339, č. - (2021), s. 12-19
856    41
$u https://pubmed.ncbi.nlm.nih.gov/33359020 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210420 $b ABA008
991    __
$a 20221025122957 $b ABA008
999    __
$a ok $b bmc $g 1649959 $s 1131808
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 339 $c - $d 12-19 $e 20201224 $i 1879-3169 $m Toxicology letters $n Toxicol Lett $x MED00004537
LZP    __
$a Pubmed-20210420

Najít záznam

Citační ukazatele

Možnosti archivace