Physicochemical and biological properties of novel amide-based steroidal inhibitors of NMDA receptors

Kód výsledku v IS VaVaI

RIV/61388963:_____/17:00474432 - isvavai.cz

Nalezeny alternativní kódy

RIV/67985823:_____/17:00474432 RIV/00216208:11120/17:43912357 RIV/00216208:11320/17:10359502

Výsledek na webu

http://dx.doi.org/10.1016/j.steroids.2016.08.010

DOI - Digital Object Identifier

10.1016/j.steroids.2016.08.010

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

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)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

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