A New Class of Potent N-Methyl-D-Aspartate Receptor Inhibitors: Sulfated Neuroactive Steroids with Lipophilic D-Ring Modifications

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F15%3A10392664" target="_blank" >RIV/00216208:11320/15:10392664 - isvavai.cz</a>
Alternative codes found
RIV/67985823:_____/15:00447623 RIV/61388963:_____/15:00447623
Result on the web
<a href="https://doi.org/10.1021/acs.jmedchem.5b00570" target="_blank" >https://doi.org/10.1021/acs.jmedchem.5b00570</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.5b00570" target="_blank" >10.1021/acs.jmedchem.5b00570</a>

Result language
angličtina
Original language name
A New Class of Potent N-Methyl-D-Aspartate Receptor Inhibitors: Sulfated Neuroactive Steroids with Lipophilic D-Ring Modifications
Original language description
N-Methyl-u-aspartate receptors (NMDARs) are glutamate-gated ion channels that play a crucial role in excitatory synaptic transmission. However, the overactivation of NMDARs can lead to excitotoxic cell damage/death, and as such, they play a role in numerous neuropathological conditions. The activity of NMDARs is known to be influenced by a wide variety of allosteric modulators, including neurosteroids, which in turn makes them promising therapeutic targets. In this study, we describe a new class of neurosteroid analogues which possess structural modifications in the steroid 1)-ring region. These analogues were tested on recombinant GluN1/GluN2B receptors to evaluate the structure activity relationship. Our results demonstrate that there is a strong correlation between this new structural feature and the in vitro activity, as all tested compounds were evaluated as more potent inhibitors of NMDA-induced currents (IC50 values varying from 90 nM to.5.4 mu M) than the known endogeneous neurosteroid pregnanolone sulfate (IC50 = 24.6 mu M).
Czech name
—
Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30103 - Neurosciences (including psychophysiology)

Project
<a href="/en/project/ED1.1.00%2F02.0109" target="_blank" >ED1.1.00/02.0109: Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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