New hybrids of tacrine and indomethacin as multifunctional acetylcholinesterase inhibitors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F21%3A10438556" target="_blank" >RIV/00216208:11160/21:10438556 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=2hKduYT2dC" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=2hKduYT2dC</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s11696-020-01295-y" target="_blank" >10.1007/s11696-020-01295-y</a>
Alternative languages
Result language
angličtina
Original language name
New hybrids of tacrine and indomethacin as multifunctional acetylcholinesterase inhibitors
Original language description
A new series of hybrid compounds were designed, consisting of anti-AChE and BuChE activity components with an anti-inflammatory component. A series of 9-amino-1,2,3,4-tetrahydroacridine and indomethacin derivatives were synthesized. All compounds were created using alkyldiamine with different chain lengths as a linker. Various biological activities were evaluated, including inhibitory activity against AChE and BuChE. The tested compounds showed high inhibitory activities against cholinesterases. The IC(50) values for all compounds ranging from 10 nM to 7 mu M. The potency of inhibition was much higher than well-known AChE and BuChE inhibitors (tacrine and donepezil). Compound3hhad the strongest inhibitory activity; kinetic studies showed it to have a mixed-type of acetylcholinesterase inhibition properties. The cytotoxicity of the newly-synthesized compounds against HepG2 (hepatocarcinoma cells) and EA.hy96 (human vein endothelial cells) cell lines was determined using the MTT and MTS tests. All investigated compounds presented similar cytotoxic activity against HepG2 and EA.hy926 cell line, ranged in micromolar values. Compounds with longer linkers showed higher antioxidant activity. The most active compound was3h. Docking studies confirmed interactions with important regions of AChE and BuChE. Its multifunctional properties, i.e. high activity against AChE and BuChE, antioxidant activity and low cytotoxicity, highlight3has a promising agent 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
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
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
Chemical Papers
ISSN
2585-7290
e-ISSN
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Volume of the periodical
75
Issue of the periodical within the volume
1
Country of publishing house
SK - SLOVAKIA
Number of pages
16
Pages from-to
249-264
UT code for WoS article
000553732100001
EID of the result in the Scopus database
2-s2.0-85088841057