Synthesis and Biological Evaluation of Novel Chromone plus Donepezil Hybrids for Alzheimer's Disease Therapy

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and Biological Evaluation of Novel Chromone plus Donepezil Hybrids for Alzheimer's Disease Therapy

Popis výsledku v původním jazyce

Background: Many factors are involved in Alzheimer&apos;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&apos;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.

Název v anglickém jazyce

Synthesis and Biological Evaluation of Novel Chromone plus Donepezil Hybrids for Alzheimer's Disease Therapy

Popis výsledku anglicky

Background: Many factors are involved in Alzheimer&apos;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&apos;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30107 - Medicinal chemistry

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Current Alzheimer research

ISSN

1567-2050

e-ISSN

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Svazek periodika

16

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

6

Strana od-do

815-820

Kód UT WoS článku

000493721100004

EID výsledku v databázi Scopus

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