Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Strong Inhibitory Effect, Low Cytotoxicity and High Plasma Stability of Steroidal Inhibitors of N-Methyl-D-Aspartate Receptors With C-3 Amide Structural Motif

SK. Adla, B. Slavikova, H. Chodounska, V. Vyklicky, M. Ladislav, P. Hubalkova, B. Krausova, T. Smejkalova, M. Nekardova, M. Smidkova, L. Monincova, R. Soucek, L. Vyklicky, E. Kudova,

. 2018 ; 9 (-) : 1299. [pub] 20181112

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19001512

Grantová podpora
NV15-29370A MZ0 CEP - Centrální evidence projektů

Herein, we report the synthesis, structure-activity relationship study, and biological evaluation of neurosteroid inhibitors of N-methyl-D-aspartate receptors (NMDARs) receptors that employ an amide structural motif, relative to pregnanolone glutamate (PAG) - a compound with neuroprotective properties. All compounds were found to be more potent NMDAR inhibitors (IC50 values varying from 1.4 to 21.7 μM) than PAG (IC50 = 51.7 μM). Selected compound 6 was evaluated for its NMDAR subtype selectivity and its ability to inhibit AMPAR/GABAR responses. Compound 6 inhibits the NMDARs (8.3 receptors (8.3 ± 2.1 μM) more strongly than it does at the GABAR and AMPARs (17.0 receptors (17.0 ± 0.2 μM and 276.4 ± 178.7 μM, respectively). In addition, compound 6 (10 μM) decreases the frequency of action potentials recorded in cultured hippocampal neurons. Next, compounds 3, 5-7, 9, and 10 were not associated with mitotoxicity, hepatotoxicity nor ROS induction. Lastly, we were able to show that all compounds have improved rat and human plasma stability over PAG.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19001512
003      
CZ-PrNML
005      
20201031115431.0
007      
ta
008      
190107s2018 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3389/fphar.2018.01299 $2 doi
035    __
$a (PubMed)30483134
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Adla, Santosh Kumar $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
245    10
$a Strong Inhibitory Effect, Low Cytotoxicity and High Plasma Stability of Steroidal Inhibitors of N-Methyl-D-Aspartate Receptors With C-3 Amide Structural Motif / $c SK. Adla, B. Slavikova, H. Chodounska, V. Vyklicky, M. Ladislav, P. Hubalkova, B. Krausova, T. Smejkalova, M. Nekardova, M. Smidkova, L. Monincova, R. Soucek, L. Vyklicky, E. Kudova,
520    9_
$a Herein, we report the synthesis, structure-activity relationship study, and biological evaluation of neurosteroid inhibitors of N-methyl-D-aspartate receptors (NMDARs) receptors that employ an amide structural motif, relative to pregnanolone glutamate (PAG) - a compound with neuroprotective properties. All compounds were found to be more potent NMDAR inhibitors (IC50 values varying from 1.4 to 21.7 μM) than PAG (IC50 = 51.7 μM). Selected compound 6 was evaluated for its NMDAR subtype selectivity and its ability to inhibit AMPAR/GABAR responses. Compound 6 inhibits the NMDARs (8.3 receptors (8.3 ± 2.1 μM) more strongly than it does at the GABAR and AMPARs (17.0 receptors (17.0 ± 0.2 μM and 276.4 ± 178.7 μM, respectively). In addition, compound 6 (10 μM) decreases the frequency of action potentials recorded in cultured hippocampal neurons. Next, compounds 3, 5-7, 9, and 10 were not associated with mitotoxicity, hepatotoxicity nor ROS induction. Lastly, we were able to show that all compounds have improved rat and human plasma stability over PAG.
655    _2
$a časopisecké články $7 D016428
700    1_
$a Slavikova, Barbora $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Chodounska, Hana $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Vyklicky, Vojtech $u Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Ladislav, Marek $u Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Hubalkova, Pavla $u Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Krausova, Barbora $u Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Smejkalova, Tereza $u Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Nekardova, Michaela $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia. Faculty of Mathematics and Physics, Charles University in Prague, Prague, Czechia.
700    1_
$a Smidkova, Marketa $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Monincova, Lenka $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Soucek, Radko $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Vyklicky, Ladislav $u Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.
700    1_
$a Kudova, Eva $u Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
773    0_
$w MED00174597 $t Frontiers in pharmacology $x 1663-9812 $g Roč. 9, č. - (2018), s. 1299
856    41
$u https://pubmed.ncbi.nlm.nih.gov/30483134 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20190107 $b ABA008
991    __
$a 20201031115430 $b ABA008
999    __
$a ind $b bmc $g 1365332 $s 1039635
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 9 $c - $d 1299 $e 20181112 $i 1663-9812 $m Frontiers in pharmacology $n Front Pharmacol $x MED00174597
GRA    __
$a NV15-29370A $p MZ0
LZP    __
$a Pubmed-20190107

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace