New hybrids of tacrine and indomethacin as multifunctional acetylcholinesterase inhibitors

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

New hybrids of tacrine and indomethacin as multifunctional acetylcholinesterase inhibitors

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

New hybrids of tacrine and indomethacin as multifunctional acetylcholinesterase inhibitors

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Chemical Papers

ISSN

2585-7290

e-ISSN

—

Svazek periodika

75

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

SK - Slovenská republika

Počet stran výsledku

16

Strana od-do

249-264

Kód UT WoS článku

000553732100001

EID výsledku v databázi Scopus

2-s2.0-85088841057