7-Methoxytacrine-Adamantylamine Heterodimers as Cholinesterase Inhibitors in Alzheimer's Disease Treatment - Synthesis, Biological Evaluation and Molecular Modeling Studies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F13%3A10133341" target="_blank" >RIV/00179906:_____/13:10133341 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/13:43874768 RIV/00216208:11160/13:10133341

Výsledek na webu

<a href="http://www.mdpi.com/1420-3049/18/2/2397" target="_blank" >http://www.mdpi.com/1420-3049/18/2/2397</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules18022397" target="_blank" >10.3390/molecules18022397</a>

Jazyk výsledku

angličtina

Název v původním jazyce

7-Methoxytacrine-Adamantylamine Heterodimers as Cholinesterase Inhibitors in Alzheimer's Disease Treatment - Synthesis, Biological Evaluation and Molecular Modeling Studies

Popis výsledku v původním jazyce

A structural series of 7-MEOTA-adamantylamine thioureas was designed, synthesized and evaluated as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). The compounds were prepared based on the multi-target-directed ligand strategy with different linker lengths (n = 2-8) joining the well-known NMDA antagonist adamantine and the hAChE inhibitor 7-methoxytacrine (7-MEOTA). Based on in silico studies, these inhibitors proved dual binding site character capable of simultaneous interaction with the peripheral anionic site (PAS) of hAChE and the catalytic active site (CAS). Clearly, these structural derivatives exhibited very good inhibitory activity towards hBChE resulting in more selective inhibitors of this enzyme. Themost potent cholinesterase inhibitor was found to be thiourea analogue 14 (with an IC50 value of 0.47 mu M for hAChE and an IC50 value of 0.11 mu M for hBChE, respectively). Molecule 14 is a suitable novel lead compound for further evalua

Název v anglickém jazyce

7-Methoxytacrine-Adamantylamine Heterodimers as Cholinesterase Inhibitors in Alzheimer's Disease Treatment - Synthesis, Biological Evaluation and Molecular Modeling Studies

Popis výsledku anglicky

A structural series of 7-MEOTA-adamantylamine thioureas was designed, synthesized and evaluated as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). The compounds were prepared based on the multi-target-directed ligand strategy with different linker lengths (n = 2-8) joining the well-known NMDA antagonist adamantine and the hAChE inhibitor 7-methoxytacrine (7-MEOTA). Based on in silico studies, these inhibitors proved dual binding site character capable of simultaneous interaction with the peripheral anionic site (PAS) of hAChE and the catalytic active site (CAS). Clearly, these structural derivatives exhibited very good inhibitory activity towards hBChE resulting in more selective inhibitors of this enzyme. Themost potent cholinesterase inhibitor was found to be thiourea analogue 14 (with an IC50 value of 0.47 mu M for hAChE and an IC50 value of 0.11 mu M for hBChE, respectively). Molecule 14 is a suitable novel lead compound for further evalua

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

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Svazek periodika

18

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

22

Strana od-do

2397-2418

Kód UT WoS článku

000315400600078

EID výsledku v databázi Scopus

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