Design, synthesis and in vitro evaluation of benzothiazole-based ureas as potential ABAD/17 beta-HSD10 modulators for Alzheimer's disease treatment

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F16%3A43875626" target="_blank" >RIV/60162694:G44__/16:43875626 - isvavai.cz</a>
Alternative codes found
RIV/62690094:18470/16:50004749 RIV/62690094:18450/16:50004749 RIV/00216208:11160/16:10326041 RIV/00179906:_____/16:10326041
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0960894X16305972" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0960894X16305972</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmcl.2016.05.087" target="_blank" >10.1016/j.bmcl.2016.05.087</a>

Result language
angličtina
Original language name
Design, synthesis and in vitro evaluation of benzothiazole-based ureas as potential ABAD/17 beta-HSD10 modulators for Alzheimer's disease treatment
Original language description
Amyloid-beta peptide (A beta) has been recognized to interact with numerous proteins, which may lead to pathological changes in cell metabolism of Alzheimer's disease (AD) patients. One such known metabolic enzyme is mitochondrial amyloid-binding alcohol dehydrogenase (ABAD), also known as 17 beta-hydroxysteroid dehydrogenase type 10 (17 beta-HSD10). Altered enzyme function caused by the A beta-ABAD interaction, was previously shown to cause mitochondrial distress and a consequent cytotoxic effect, therefore providing a feasible target in AD drug development. Based on previous frentizole derivatives studies, we report two novel series of benzothiazolyl ureas along with novel insights into the structure and activity relationships for inhibition of ABAD. Two compounds (37, 39) were identified as potent ABAD inhibitors, where compound 39 exhibited comparable cytotoxicity with the frentizole standard; however, one-fold higher cytotoxicity than the parent riluzole standard. The calculated and experimental physical chemical properties of the most potent compounds showed promising features for blood-brain barrier penetration.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Project
<a href="/en/project/NV15-28967A" target="_blank" >NV15-28967A: Modulators of mitochondrial enzymes for treatment of neurodegenerative disorders</a><br>
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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