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Novel Benzothiazole-based Ureas as 17β-HSD10 Inhibitors, A Potential Alzheimer's Disease Treatment
L. Aitken, O. Benek, BE. McKelvie, RE. Hughes, L. Hroch, M. Schmidt, LL. Major, L. Vinklarova, K. Kuca, TK. Smith, K. Musilek, FJ. Gunn-Moore,
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
CZ.02.1.01/0.0/0.0/18_069/0010054
Ministry of Education, Youth and Sports of Czech Republic
Faculty of Science, no. VT2019-2021, SV2115-2018
University of Hradec Kralove
40th Anniversary Award
RS MacDonald Charitable Trust
291
Alzheimer's Society - United Kingdom
ISSF3 University of St Andrews
WT-ISSF
A2216
Rosetrees Trust
NLK
Directory of Open Access Journals
od 1997
Free Medical Journals
od 1997
PubMed Central
od 2001
Europe PubMed Central
od 2001
ProQuest Central
od 1997-01-01
Open Access Digital Library
od 1997-01-01
Medline Complete (EBSCOhost)
od 2009-03-01
Health & Medicine (ProQuest)
od 1997-01-01
- MeSH
- 17-hydroxysteroidní dehydrogenasy antagonisté a inhibitory chemie MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- amyloidní beta-protein metabolismus MeSH
- benzothiazoly chemie MeSH
- buněčné linie MeSH
- lidé MeSH
- mitochondrie metabolismus MeSH
- močovina chemie MeSH
- molekulární struktura MeSH
- racionální návrh léčiv MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
: 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 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10), also known as amyloid-binding alcohol dehydrogenase (ABAD). We and others have shown that frentizole and riluzole derivatives can inhibit 17β-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 17β-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.
Biomedical Science Research Complex University of St Andrews North Haugh St Andrews KY16 9ST UK
University Hospital Biomedical Research Center Sokolska 581 500 05 Hradec Kralove Czech Republic
Citace poskytuje Crossref.org
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