6-benzothiazolyl ureas, thioureas and guanidines are potent inhibitors of ABAD/17 beta-HSD10 and potential drugs for Alzheimer's disease treatment: design, synthesis and in vitro evaluation
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F17%3A43875755" target="_blank" >RIV/60162694:G44__/17:43875755 - isvavai.cz</a>
Alternative codes found
RIV/62690094:18470/17:50013416 RIV/00216208:11160/17:10360343 RIV/00179906:_____/17:10360343
Result on the web
<a href="http://www.eurekaselect.com/149078/article" target="_blank" >http://www.eurekaselect.com/149078/article</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1573406413666170109142725" target="_blank" >10.2174/1573406413666170109142725</a>
Alternative languages
Result language
angličtina
Original language name
6-benzothiazolyl ureas, thioureas and guanidines are potent inhibitors of ABAD/17 beta-HSD10 and potential drugs for Alzheimer's disease treatment: design, synthesis and in vitro evaluation
Original language description
Background: The mitochondrial enzyme amyloid beta-binding alcohol dehydrogenase (ABAD) also known as 17 beta-hydroxysteroid dehydrogenase type 10 (17 beta-HSD10) has been connected with the pathogenesis of Alzheimer's disease (AD). ABAD/17 beta-HSD10 is a binding site for the amyloid-beta peptide (A beta) inside the mitochondrial matrix where it exacerbates A beta toxicity. Interaction between these two proteins triggers a series of events leading to mitochondrial dysfunction as seen in AD. Methods: As ABAD's enzymatic activity is required for mediating A beta toxicity, its inhibition presents a promising strategy for AD treatment. In this study, a series of new benzothiazolylurea analogues have been prepared and evaluated in vitro for their potency to inhibit ABAD/17 beta-HSD10 enzymatic activity. The most potent compounds have also been tested for their cytotoxic properties and their ability to permeate through blood-brain barrier has been predicted. To explain the structure-activity relationship QSAR and pharmacophore studies have been performed. Results and Conclusion: Compound 12 was identified being the most promising hit compound with good inhibitory activity (IC50 = 3.06 +/- 0.40 mu M) and acceptable cytotoxicity profile comparable to the parent compound of frentizole. The satisfactory physical-chemical properties suggesting its capability to permeate through BBB make compound 12 a novel lead structure for further development and biological assessment.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Medicinal Chemistry
ISSN
1573-4064
e-ISSN
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Volume of the periodical
13
Issue of the periodical within the volume
4
Country of publishing house
AE - UNITED ARAB EMIRATES
Number of pages
14
Pages from-to
345-358
UT code for WoS article
000402479000004
EID of the result in the Scopus database
2-s2.0-85020833089