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dc.contributor.authorAitken, Laura
dc.contributor.authorBenek, Ondrej
dc.contributor.authorMcKelvie, Brogan
dc.contributor.authorHughes, Rebecca E.
dc.contributor.authorHroch, Lukas
dc.contributor.authorSchmidt, Monika
dc.contributor.authorMajor, Louise L
dc.contributor.authorVinklarova, Lucie
dc.contributor.authorKuca, Kamil
dc.contributor.authorSmith, Terry K
dc.contributor.authorMusilek, Kamil
dc.contributor.authorGunn-Moore, Frank J
dc.date.accessioned2019-07-30T08:30:04Z
dc.date.available2019-07-30T08:30:04Z
dc.date.issued2019-07-29
dc.identifier.citationAitken , L , Benek , O , McKelvie , B , Hughes , R E , Hroch , L , Schmidt , M , Major , L L , Vinklarova , L , Kuca , K , Smith , T K , Musilek , K & Gunn-Moore , F J 2019 , ' Novel benzothiazole-based ureas as 17β-HSD10 inhibitors, a potential Alzheimer’s disease treatment ' , Molecules , vol. 24 , no. 15 , 2757 . https://doi.org/10.3390/molecules24152757en
dc.identifier.issn1420-3049
dc.identifier.otherPURE: 260299059
dc.identifier.otherPURE UUID: d4b2522b-c8b3-4f58-8d49-afda62a22d5a
dc.identifier.otherORCID: /0000-0001-5287-4488/work/60195453
dc.identifier.otherORCID: /0000-0003-3422-3387/work/60195495
dc.identifier.otherORCID: /0000-0001-7259-4491/work/60195924
dc.identifier.otherWOS: 000482441100080
dc.identifier.otherScopus: 85070791027
dc.identifier.urihttp://hdl.handle.net/10023/18200
dc.descriptionFunding: This work was supported by Alzheimer’s Society (specifically The Barcopel Foundation), Scottish Universities Life Science Alliance (SULSA), The Rosetrees Trust, WT-ISSF and RS MacDonald Charitable Trust, Ministry of Education, Youth and Sports of Czech Republic (project ESF no. CZ.02.1.01/0.0/0.0/18_069/0010054), and University of Hradec Kralove (Faculty of Science, no. VT2019-2021, SV2115-2018, and Postdoctoral job positions at UHK).en
dc.description.abstractIt 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.
dc.language.isoeng
dc.relation.ispartofMoleculesen
dc.rights© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectAlzheimer's disease (AD)en
dc.subjectAmyloid-beta peptide (Aβ)en
dc.subjectMitochondriaen
dc.subjectAmyloid binding alcohol dehydrogenase (ABAD)en
dc.subject17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10)en
dc.subjectBenzothiazoleen
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectDASen
dc.subject.lccQDen
dc.subject.lccQH301en
dc.subject.lccRC0321en
dc.titleNovel benzothiazole-based ureas as 17β-HSD10 inhibitors, a potential Alzheimer’s disease treatmenten
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews.Institute of Behavioural and Neural Sciencesen
dc.identifier.doihttps://doi.org/10.3390/molecules24152757
dc.description.statusPeer revieweden


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