2,3-Dihydro-1H-cyclopenta[b]quinoline Derivatives as Acetylcholinesterase Inhibitors-Synthesis, Radiolabeling and Biodistribution
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F12%3A10124220" target="_blank" >RIV/00216208:11160/12:10124220 - isvavai.cz</a>
Výsledek na webu
<a href="http://www.mdpi.com/1422-0067/13/8/10067/pdf" target="_blank" >http://www.mdpi.com/1422-0067/13/8/10067/pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms130810067" target="_blank" >10.3390/ijms130810067</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
2,3-Dihydro-1H-cyclopenta[b]quinoline Derivatives as Acetylcholinesterase Inhibitors-Synthesis, Radiolabeling and Biodistribution
Popis výsledku v původním jazyce
In the present study we describe the synthesis and biological assessment of new tacrine analogs in the course of inhibition of acetylcholinesterase. The obtained molecules were synthesized in a condensation reaction between activated 6-BOC-hydrazinopyridine-3-carboxylic acid and 8-aminoalkyl derivatives of 2,3-dihydro-1H-cyclopenta[b]quinoline. Activities of the newly synthesized compounds were estimated by means of Ellman's method. Compound 6h (IC50 = 3.65 nM) was found to be most active. All obtainednovel compounds present comparable activity to that of tacrine towards acetylcholinesterase (AChE) and, simultaneously, lower activity towards butyrylcholinesterase (BChE). Apart from 6a, all synthesized compounds are characterized by a higher affinity for AChE and a lower affinity for BChE in comparison with tacrine. Among all obtained molecules, compound 6h presented the highest selectivity towards inhibition of acetylcholinesterase. Molecular modeling showed that all compounds demonst
Název v anglickém jazyce
2,3-Dihydro-1H-cyclopenta[b]quinoline Derivatives as Acetylcholinesterase Inhibitors-Synthesis, Radiolabeling and Biodistribution
Popis výsledku anglicky
In the present study we describe the synthesis and biological assessment of new tacrine analogs in the course of inhibition of acetylcholinesterase. The obtained molecules were synthesized in a condensation reaction between activated 6-BOC-hydrazinopyridine-3-carboxylic acid and 8-aminoalkyl derivatives of 2,3-dihydro-1H-cyclopenta[b]quinoline. Activities of the newly synthesized compounds were estimated by means of Ellman's method. Compound 6h (IC50 = 3.65 nM) was found to be most active. All obtainednovel compounds present comparable activity to that of tacrine towards acetylcholinesterase (AChE) and, simultaneously, lower activity towards butyrylcholinesterase (BChE). Apart from 6a, all synthesized compounds are characterized by a higher affinity for AChE and a lower affinity for BChE in comparison with tacrine. Among all obtained molecules, compound 6h presented the highest selectivity towards inhibition of acetylcholinesterase. Molecular modeling showed that all compounds demonst
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
FR - Farmakologie a lékárnická chemie
OECD FORD obor
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Návaznosti výsledku
Projekt
<a href="/cs/project/GAP304%2F10%2F1738" target="_blank" >GAP304/10/1738: Radioaktivně značené neuropeptidy cílené pro diagnostiku a terapii nádorů</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2012
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
International Journal of Molecular Sciences
ISSN
1661-6596
e-ISSN
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Svazek periodika
13
Číslo periodika v rámci svazku
8
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
24
Strana od-do
10067-10090
Kód UT WoS článku
000308243400045
EID výsledku v databázi Scopus
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