Preparation, in vitro evaluation and molecular modelling of pyridinium-quinolinium/isoquinolinium non-symmetrical bisquaternary cholinesterase inhibitors
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F13%3A10146074" target="_blank" >RIV/00179906:_____/13:10146074 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/60162694:G44__/13:43874907 RIV/62690094:18470/13:50001650 RIV/44555601:13440/13:43885136 RIV/00216208:11160/13:10146074
Výsledek na webu
<a href="http://www.sciencedirect.com/science/article/pii/S0960894X13012493" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0960894X13012493</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmcl.2013.10.043" target="_blank" >10.1016/j.bmcl.2013.10.043</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Preparation, in vitro evaluation and molecular modelling of pyridinium-quinolinium/isoquinolinium non-symmetrical bisquaternary cholinesterase inhibitors
Popis výsledku v původním jazyce
Two series of non-symmetrical bisquaternary pyridinium-quinolinium and pyridinium-isoquinolinium compounds were prepared as molecules potentially applicable in myasthenia gravis treatment. Their inhibitory ability towards human recombinant acetylcholinesterase and human plasmatic butyrylcholinesterase was determined and the results were compared to the known effective inhibitors such as ambenonium dichloride, edrophonium bromide and experimental compound BW284C51. Two compounds, 1-(10-(pyridinium-1-yl)decyl)quinolinium dibromide and 1-(12-(pyridinium-1-yl)dodecyl)quinolinium dibromide, showed very promising affinity for acetylcholinesterase with their IC50 values reaching nM inhibition of acetylcholinesterase. These most active compounds also showed satisfactory selectivity towards acetylcholinesterase and they seem to be very promising as leading structures for further modifications and optimization. Two of the most promising compounds were examined in the molecular modelling study in
Název v anglickém jazyce
Preparation, in vitro evaluation and molecular modelling of pyridinium-quinolinium/isoquinolinium non-symmetrical bisquaternary cholinesterase inhibitors
Popis výsledku anglicky
Two series of non-symmetrical bisquaternary pyridinium-quinolinium and pyridinium-isoquinolinium compounds were prepared as molecules potentially applicable in myasthenia gravis treatment. Their inhibitory ability towards human recombinant acetylcholinesterase and human plasmatic butyrylcholinesterase was determined and the results were compared to the known effective inhibitors such as ambenonium dichloride, edrophonium bromide and experimental compound BW284C51. Two compounds, 1-(10-(pyridinium-1-yl)decyl)quinolinium dibromide and 1-(12-(pyridinium-1-yl)dodecyl)quinolinium dibromide, showed very promising affinity for acetylcholinesterase with their IC50 values reaching nM inhibition of acetylcholinesterase. These most active compounds also showed satisfactory selectivity towards acetylcholinesterase and they seem to be very promising as leading structures for further modifications and optimization. Two of the most promising compounds were examined in the molecular modelling study in
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/EE2.3.20.0235" target="_blank" >EE2.3.20.0235: Vybudování výzkumného týmu experimentální a aplikované biofarmacie</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2013
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Bioorganic and Medicinal Chemistry Letters
ISSN
0960-894X
e-ISSN
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Svazek periodika
23
Číslo periodika v rámci svazku
24
Stát vydavatele periodika
BR - Brazilská federativní republika
Počet stran výsledku
4
Strana od-do
6663-6666
Kód UT WoS článku
000327787700026
EID výsledku v databázi Scopus
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