Synthesis and Biological Evaluation of Novel Chromone plus Donepezil Hybrids for Alzheimer's Disease Therapy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F19%3A50016252" target="_blank" >RIV/62690094:18470/19:50016252 - isvavai.cz</a>
Result on the web
<a href="http://www.eurekaselect.com/175574/article" target="_blank" >http://www.eurekaselect.com/175574/article</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1567205016666191011112624" target="_blank" >10.2174/1567205016666191011112624</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis and Biological Evaluation of Novel Chromone plus Donepezil Hybrids for Alzheimer's Disease Therapy
Original language description
Background: Many factors are involved in Alzheimer's Disease (AD) such as amyloid plaques, neurofibrillary tangles, cholinergic deficit and oxidative stress. To counter the complexity of the disease the new approach for drug development is to create a single molecule able to act simultaneously on different targets. Objective: We conceived eight drug likeliness compounds targeting the inhibition of cholinesterases and the scavenging of radicals. Methods: We synthesised the new molecules by the Passerini multicomponent reaction and evaluated their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) as well as their antioxidant activities by the Oxygen Radical Absorbance Capacity (ORAC) assay. The lipinski's rule for drug likeness and in silico ADME prediction was also performed. Results: Compounds 4f [IC50 (EeAChE) = 0.30 mu M; IC50 (eqBuChE) = 0.09 mu M; ORAC = 0.64 TE] and 4h [IC50 (EeAChE) = 1 mu M; IC50 ( eqBuChE) = 0.03 mu M; ORAC = 0.50 TE] were identified as hits for further development. Conclusion: The Passerini reaction allowed us the facile synthesis of ditarget molecules of interest for the treatment of AD.
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
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Current Alzheimer research
ISSN
1567-2050
e-ISSN
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Volume of the periodical
16
Issue of the periodical within the volume
9
Country of publishing house
AE - UNITED ARAB EMIRATES
Number of pages
6
Pages from-to
815-820
UT code for WoS article
000493721100004
EID of the result in the Scopus database
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