Physicochemical and biological properties of novel amide-based steroidal inhibitors of NMDA receptors
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00474432" target="_blank" >RIV/61388963:_____/17:00474432 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/67985823:_____/17:00474432 RIV/00216208:11120/17:43912357 RIV/00216208:11320/17:10359502
Výsledek na webu
<a href="http://dx.doi.org/10.1016/j.steroids.2016.08.010" target="_blank" >http://dx.doi.org/10.1016/j.steroids.2016.08.010</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.steroids.2016.08.010" target="_blank" >10.1016/j.steroids.2016.08.010</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Physicochemical and biological properties of novel amide-based steroidal inhibitors of NMDA receptors
Popis výsledku v původním jazyce
Herein, we report a new class of amide-based inhibitors (1-4) of N-methyl-o-aspartate receptors (NMDARs) that were prepared as analogues of pregnanolone sulfate (PAS) and pregnanolone glutamate (PAG) - the steroidal neuroprotective NMDAR inhibitors. A series of experiments were conducted to evaluate their physicochemical and biological properties: (i) the inhibitory effect of compounds 3 and 4 on NMDARs was significantly improved (IC50 = 1.0 and 1.4 mu M respectively) as compared with endogenous inhibitor - pregnanolone sulfate (IC50 = 24.6 mu M) and pregnanolone glutamate (IC50 = 51.7 mu M), (ii) physicochemical properties (logP and logD) were calculated, (iii) Caco-2 assay revealed that the permeability properties of compounds 2 and 4 are comparable with pregnanolone glutamate, (iv) compounds 1-4 have minimal or no adverse hepatic effect, (v) compounds 1-4 cross blood-brain-barrier.
Název v anglickém jazyce
Physicochemical and biological properties of novel amide-based steroidal inhibitors of NMDA receptors
Popis výsledku anglicky
Herein, we report a new class of amide-based inhibitors (1-4) of N-methyl-o-aspartate receptors (NMDARs) that were prepared as analogues of pregnanolone sulfate (PAS) and pregnanolone glutamate (PAG) - the steroidal neuroprotective NMDAR inhibitors. A series of experiments were conducted to evaluate their physicochemical and biological properties: (i) the inhibitory effect of compounds 3 and 4 on NMDARs was significantly improved (IC50 = 1.0 and 1.4 mu M respectively) as compared with endogenous inhibitor - pregnanolone sulfate (IC50 = 24.6 mu M) and pregnanolone glutamate (IC50 = 51.7 mu M), (ii) physicochemical properties (logP and logD) were calculated, (iii) Caco-2 assay revealed that the permeability properties of compounds 2 and 4 are comparable with pregnanolone glutamate, (iv) compounds 1-4 have minimal or no adverse hepatic effect, (v) compounds 1-4 cross blood-brain-barrier.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10401 - Organic chemistry
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2017
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Steroids
ISSN
0039-128X
e-ISSN
—
Svazek periodika
117
Číslo periodika v rámci svazku
Jan
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
10
Strana od-do
52-61
Kód UT WoS článku
000392566800009
EID výsledku v databázi Scopus
2-s2.0-84994181912