7-MEOTA-donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F14%3A10218487" target="_blank" >RIV/00216208:11310/14:10218487 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/14:43875093 RIV/00023752:_____/14:43914586 RIV/62690094:18470/14:50002441 RIV/00216208:11160/14:10218487 RIV/00179906:_____/14:10218487

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0223523414004905" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0223523414004905</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2014.05.066" target="_blank" >10.1016/j.ejmech.2014.05.066</a>

Jazyk výsledku

angličtina

Název v původním jazyce

7-MEOTA-donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies

Popis výsledku v původním jazyce

A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (EeAChE), human recombinant AChE (hAChE), equine serum butyrylcholinesterase (eqBChE) and human plasmatic BChE (hBChE). New hybrids consist of a 7-MEOTA unit, representing less toxic tacrine (THA) derivative, connected with analogues of N-benzylpiperazine moieties mimicking N-benzylpiperidine fragment from donepezil. 7-MEOTA-donepezil like compounds exerted mostly non-selective profile in inhibiting cholinesterases of different origin with IC50 ranging from micromolar to sub-micromolar concentration scale. Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors are capable to simultaneously bind peripheral anionic site (PAS) as well as catalytic anionic site (CAS) of AChE. Molecular modeling studies and QSAR studies were performed to rationalize studies from in vitro. Overall, 7-MEOTA-donepezil like deri

Název v anglickém jazyce

7-MEOTA-donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies

Popis výsledku anglicky

A novel series of 7-methoxytacrine (7-MEOTA)-donepezil like compounds was synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (EeAChE), human recombinant AChE (hAChE), equine serum butyrylcholinesterase (eqBChE) and human plasmatic BChE (hBChE). New hybrids consist of a 7-MEOTA unit, representing less toxic tacrine (THA) derivative, connected with analogues of N-benzylpiperazine moieties mimicking N-benzylpiperidine fragment from donepezil. 7-MEOTA-donepezil like compounds exerted mostly non-selective profile in inhibiting cholinesterases of different origin with IC50 ranging from micromolar to sub-micromolar concentration scale. Kinetic analysis confirmed mixed-type inhibition presuming that these inhibitors are capable to simultaneously bind peripheral anionic site (PAS) as well as catalytic anionic site (CAS) of AChE. Molecular modeling studies and QSAR studies were performed to rationalize studies from in vitro. Overall, 7-MEOTA-donepezil like deri

Druh

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

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GAP303%2F11%2F1907" target="_blank" >GAP303/11/1907: Nové inhibitory acetylcholinesterasy odvozené od látky 7-MEOTA - potenciální léčiva pro Alzheimerovu nemoc</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

—

Svazek periodika

82

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

13

Strana od-do

426-438

Kód UT WoS článku

000339039100040

EID výsledku v databázi Scopus

—