6-Benzothiazolyl ureas, thioureas and guanidines are potent inhibitors of ABAD/17-HSD10 and potential drugs for Alzheimer's disease treatment: Design, synthesis and in vitro evaluation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F17%3A43915455" target="_blank" >RIV/00023752:_____/17:43915455 - isvavai.cz</a>

Alternative codes found

RIV/00007064:K13__/17:N0000036

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>

Result language

angličtina

Original language name

6-Benzothiazolyl ureas, thioureas and guanidines are potent inhibitors of ABAD/17-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 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) has been connected with the pathogenesis of Alzheimer’s disease (AD). ABAD/17β-HSD10 is a binding site for the amyloid-beta peptide (Aβ) inside the mitochondrial matrix where it exacerbates Aβtoxicity. 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 Aβ 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/17β-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 structureactivity 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 µ 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

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30107 - Medicinal chemistry

Project

<a href="/en/project/LO1611" target="_blank" >LO1611: Sustainability for The National Institute of Mental Health</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Medicinal Chemistry

ISSN

1573-4064

e-ISSN

—

Volume of the periodical

13

Issue of the periodical within the volume

4

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

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