N-Substituted 3-Aminooxindoles and N-Propargyl Derivatives: Potential Biological Activities against Alzheimer's Disease

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50022162" target="_blank" >RIV/62690094:18470/23:50022162 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S2211715623002710?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2211715623002710?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.rechem.2023.101032" target="_blank" >10.1016/j.rechem.2023.101032</a>

Result language

angličtina

Original language name

N-Substituted 3-Aminooxindoles and N-Propargyl Derivatives: Potential Biological Activities against Alzheimer's Disease

Original language description

The oxindole core is an important structural motif in many natural and synthetic substances with various biological activities including anticancer, antineurodegenerative, and antimicrobial properties. This report focuses on the synthesis and biological activity of a series of novel N-substituted 3-aminooxindoles and their assessment in cholinesterase (ChE) and monoamine oxidase (MAO) inhibition. With regard to MAO inhibition, a series of N- propargyl containing derivatives was synthesized and screened. Despite being weak inhibitors of MAO-A and MAO-B, the compounds were selective for butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE). Most of them were strong inhibitors of BuChE with IC50&apos;s of less than 1 &amp; mu;M, and one compound showed an IC50 = 27 nM. The mechanism of action of the inhibition was pin-pointed through molecular modeling, and was validated using saturation-transfer-difference (STD) NMR. Some of the compounds were screened for anti-oxidant properties, but showed no activity. The same compounds were screened in the neurodegenerative disease model cell-line SH-SY5Y and although some were found to be non-cytotoxic, others were moderately cytotoxic. Continuous live cell imaging experiments showed that the compounds do not induce relevant cell damage and thus, the compounds might be interesting drug candidates for Alzheimer&apos;s disease. Furthermore, the most active compounds showed excellent drug-likeness and pharmacological properties predicted using Swiss-ADME, and the pharmacokinetic simulations indicated that all these compounds cross the blood-brain-barrier.

Czech name

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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

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OECD FORD branch

30107 - Medicinal chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

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

Name of the periodical

RESULTS IN CHEMISTRY

ISSN

2211-7156

e-ISSN

—

Volume of the periodical

6

Issue of the periodical within the volume

December

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

13

Pages from-to

"Article Number: 101032"

UT code for WoS article

001065875600001

EID of the result in the Scopus database

2-s2.0-85167966806