Evaluation of Novel Substituted Furopyridines as Inhibitors of Protein Kinases Related to Tau Pathology in Alzheimer's Disease
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F21%3A73610750" target="_blank" >RIV/61989592:15310/21:73610750 - isvavai.cz</a>
Result on the web
<a href="https://obd.upol.cz/id_publ/333190637" target="_blank" >https://obd.upol.cz/id_publ/333190637</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1573406417666210601144510" target="_blank" >10.2174/1573406417666210601144510</a>
Alternative languages
Result language
angličtina
Original language name
Evaluation of Novel Substituted Furopyridines as Inhibitors of Protein Kinases Related to Tau Pathology in Alzheimer's Disease
Original language description
Background: Alzheimer's disease (AD) is characterized by a progressive neuronal degeneration caused by two pathological hallmarks, hyperphosphorylated tau protein aggregated into tau filaments and amyloid precursor protein derived beta amyloid peptides aggregated into extracellular amyloid plaques. All attempts so far to find effective drugs failed in clinical trials. AD is a multifactorial disease, so that selective drugs to target one AD-relevant structure alone may not be sufficient. Objective: We built novel furopyridines with various substitution patterns to evaluate them as protein kinases inhibitors of enzymes related to tau pathology. Method: Furopyridine derivatives were synthesized and purified using column chromatography. The protein kinase inhibitory properties were determined in ATP-competition assays with determined affinity constants for the most active compounds. Results: The compounds were prepared in simple two-component reactions of substituted 1,4-dihydropyridines and respective quinones to obtain various substitutions of the molecular furopyridine scaffold. The substituent effects on the determined kinase inhibitory properties of cdk1, cdk2, Fyn, JNK3 and gsk-3 beta are discussed. Conclusion: Various 3-substitutions were found most sensitive for the protein kinase inhibition depending on the length, nature and a substituent positioning within. We identified compounds as inhibitors of several kinases as a tool to potentially combat the disease progress in a multitargeting approach.
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
30107 - Medicinal chemistry
Result continuities
Project
<a href="/en/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molecular, cellular and clinical approach to healthy ageing</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
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
17
Issue of the periodical within the volume
8
Country of publishing house
AE - UNITED ARAB EMIRATES
Number of pages
12
Pages from-to
844-855
UT code for WoS article
000677684900004
EID of the result in the Scopus database
2-s2.0-85116958433