St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Register / Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Novel benzothiazole-based ureas as 17β-HSD10 inhibitors, a potential Alzheimer’s disease treatment

Thumbnail
View/Open
Aitken_2019_Mol_NovelBenzothiazole_basedUreas_CCBY_VoR.pdf (968.4Kb)
Date
29/07/2019
Author
Aitken, Laura
Benek, Ondrej
McKelvie, Brogan
Hughes, Rebecca E.
Hroch, Lukas
Schmidt, Monika
Major, Louise L
Vinklarova, Lucie
Kuca, Kamil
Smith, Terry K
Musilek, Kamil
Gunn-Moore, Frank J
Funder
The Wellcome Trust
Grant ID
097831/z/11/z
Keywords
Alzheimer's disease (AD)
Amyloid-beta peptide (Aβ)
Mitochondria
Amyloid binding alcohol dehydrogenase (ABAD)
17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10)
Benzothiazole
QD Chemistry
QH301 Biology
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
DAS
Metadata
Show full item record
Abstract
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.
Citation
Aitken , 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/molecules24152757
Publication
Molecules
Status
Peer reviewed
DOI
https://doi.org/10.3390/molecules24152757
ISSN
1420-3049
Type
Journal article
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/).
Description
Funding: 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).
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/18200

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter