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Benzothiazolyl ureas are low micromolar and uncompetitive inhibitors of 17β-HSD10 with implications to Alzheimer’s disease treatment
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dc.contributor.author | Schmidt, Monika | |
dc.contributor.author | Benek, Ondrej | |
dc.contributor.author | Vinklarova, Lucie | |
dc.contributor.author | Hrabinova, Martina | |
dc.contributor.author | Zemanova, Lucie | |
dc.contributor.author | Chribek, Matej | |
dc.contributor.author | Kralova, Vendula | |
dc.contributor.author | Hroch, Lukas | |
dc.contributor.author | Dolezal, Rafael | |
dc.contributor.author | Lycka, Antonin | |
dc.contributor.author | Prchal, Lukas | |
dc.contributor.author | Jun, Daniel | |
dc.contributor.author | Aitken, Laura | |
dc.contributor.author | Gunn-Moore, Frank | |
dc.contributor.author | Kuca, Kamil | |
dc.contributor.author | Musilek, Kamil | |
dc.date.accessioned | 2020-04-02T15:30:04Z | |
dc.date.available | 2020-04-02T15:30:04Z | |
dc.date.issued | 2020-03-17 | |
dc.identifier | 267148402 | |
dc.identifier | fe3e8a12-af8f-43dc-8cc7-8264132d98af | |
dc.identifier | 85082088815 | |
dc.identifier | 000529890200155 | |
dc.identifier.citation | Schmidt , M , Benek , O , Vinklarova , L , Hrabinova , M , Zemanova , L , Chribek , M , Kralova , V , Hroch , L , Dolezal , R , Lycka , A , Prchal , L , Jun , D , Aitken , L , Gunn-Moore , F , Kuca , K & Musilek , K 2020 , ' Benzothiazolyl ureas are low micromolar and uncompetitive inhibitors of 17β-HSD10 with implications to Alzheimer’s disease treatment ' , International Journal of Molecular Sciences , vol. 21 , no. 6 , 2059 . https://doi.org/10.3390/ijms21062059 | en |
dc.identifier.issn | 1422-0067 | |
dc.identifier.other | Bibtex: ijms21062059 | |
dc.identifier.other | ORCID: /0000-0003-3422-3387/work/71559566 | |
dc.identifier.other | ORCID: /0000-0001-7259-4491/work/71559872 | |
dc.identifier.uri | https://hdl.handle.net/10023/19746 | |
dc.description | This research was funded by Ministry of Health of the Czech Republic (no. NV19-09-00578), Ministry of Education, Youth and Sports of the Czech Republic (project ESF no. CZ.02.1.01/0.0/0.0/18_069/0010054), University of Hradec Kralove (Faculty of Science, no. VT2019-2021, SV2115-2018, and Postdoctoral job positions at UHK), University Hospital Hradec Kralove (UHHK, 00179906), National Institute of Mental Health (NIMH-CZ) project no. LO1611 for financial support from MEYS under the program of NPU I, Wellcome Trust (204821/Z/16/Z), The Rosetrees Trust, and the RS MacDonald Charitable Trust. | en |
dc.description.abstract | Human 17β-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson’s disease, or Alzheimer’s disease, in which it was shown to interact with the amyloid-beta peptide. We prepared approximately 60 new compounds based on a benzothiazolyl scaffold and evaluated their inhibitory ability and mechanism of action. The most potent inhibitors contained 3-chloro and 4-hydroxy substitution on the phenyl ring moiety, a small substituent at position 6 on the benzothiazole moiety, and the two moieties were connected via a urea linker ( 4at , 4bb , and 4bg ). These compounds exhibited IC50 values of 1–2 μM and showed an uncompetitive mechanism of action with respect to the substrate, acetoacetyl-CoA. These uncompetitive benzothiazolyl inhibitors of 17β-hydroxysteroid dehydrogenase type 10 are promising compounds for potential drugs for neurodegenerative diseases that warrant further research and development. | |
dc.format.extent | 26 | |
dc.format.extent | 2983343 | |
dc.language.iso | eng | |
dc.relation.ispartof | International Journal of Molecular Sciences | en |
dc.subject | Neurodegeneration | en |
dc.subject | Alzheimer’s disease | en |
dc.subject | 17β-hydroxysteroid dehydrogenase type 10 | en |
dc.subject | ABAD | en |
dc.subject | Inhibitor | en |
dc.subject | Benzothiazole | en |
dc.subject | QH301 Biology | en |
dc.subject | NDAS | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | QH301 | en |
dc.title | Benzothiazolyl ureas are low micromolar and uncompetitive inhibitors of 17β-HSD10 with implications to Alzheimer’s disease treatment | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Wellcome Trust | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Centre for Biophotonics | en |
dc.contributor.institution | University of St Andrews. Institute of Behavioural and Neural Sciences | en |
dc.identifier.doi | 10.3390/ijms21062059 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | 204821/Z/16/Z | en |
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