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A novel urea derivative anticonvulsant: In vivo biological evaluation, radioreceptor analysis of GABAA receptors and molecular docking studies of enantiomers

Tamara Vladimirovna Shushpanova 1
Tamara Vladimirovna Shushpanova
, 
Nikolay Aleksandrovich Bokhan 1, 2
Nikolay Aleksandrovich Bokhan
,  , 
Victoria V Shtrykova 3
Victoria V Shtrykova
, 
Olga V Shushpanova 4
Olga V Shushpanova
, 
Vladimir V Udut 5
Vladimir V Udut
1 Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation
2 Siberian State Medical University, Tomsk, Russian Federation
3 National Research Tomsk Polytechnic University, Tomsk, Russian Federation
4 Scientific Center for Mental Health, Moscow, Russian Federation
5 E.D. Goldberg Scientific Research Institute of Pharmacology and Regenerative Medicine, Tomsk Research Center, Russian Academy of Sciences, Tomsk, Russian Federation
10.1016/j.mencom.2023.06.034
Published 2023-06-13
Communication , Volume 33, Issue 4, 546-549
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Shushpanova T. V. et al. A novel urea derivative anticonvulsant: In vivo biological evaluation, radioreceptor analysis of GABAA receptors and molecular docking studies of enantiomers // Mendeleev Communications. 2023. Vol. 33. No. 4. pp. 546-549.
GOST all authors (up to 50) Copy
Shushpanova T. V., Bokhan N. A., Kuksenok V. Y., Shtrykova V. V., Shushpanova O. V., Udut V. V. A novel urea derivative anticonvulsant: In vivo biological evaluation, radioreceptor analysis of GABAA receptors and molecular docking studies of enantiomers // Mendeleev Communications. 2023. Vol. 33. No. 4. pp. 546-549.
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TY - JOUR
DO - 10.1016/j.mencom.2023.06.034
UR - https://mendcomm.colab.ws/publications/10.1016/j.mencom.2023.06.034
TI - A novel urea derivative anticonvulsant: In vivo biological evaluation, radioreceptor analysis of GABAA receptors and molecular docking studies of enantiomers
T2 - Mendeleev Communications
AU - Shushpanova, Tamara Vladimirovna
AU - Bokhan, Nikolay Aleksandrovich
AU - Kuksenok, Vera Yur'evna
AU - Shtrykova, Victoria V
AU - Shushpanova, Olga V
AU - Udut, Vladimir V
PY - 2023
DA - 2023/06/13
PB - Mendeleev Communications
SP - 546-549
IS - 4
VL - 33
ER -
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@article{2023_Shushpanova,
author = {Tamara Vladimirovna Shushpanova and Nikolay Aleksandrovich Bokhan and Vera Yur'evna Kuksenok and Victoria V Shtrykova and Olga V Shushpanova and Vladimir V Udut},
title = {A novel urea derivative anticonvulsant: In vivo biological evaluation, radioreceptor analysis of GABAA receptors and molecular docking studies of enantiomers},
journal = {Mendeleev Communications},
year = {2023},
volume = {33},
publisher = {Mendeleev Communications},
month = {Jun},
url = {https://mendcomm.colab.ws/publications/10.1016/j.mencom.2023.06.034},
number = {4},
pages = {546--549},
doi = {10.1016/j.mencom.2023.06.034}
}
MLA
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Shushpanova, Tamara Vladimirovna, et al. “A novel urea derivative anticonvulsant: In vivo biological evaluation, radioreceptor analysis of GABAA receptors and molecular docking studies of enantiomers.” Mendeleev Communications, vol. 33, no. 4, Jun. 2023, pp. 546-549. https://mendcomm.colab.ws/publications/10.1016/j.mencom.2023.06.034.

Keywords

anticonvulsants
enantiomers.
GABAA receptor
molecular docking
γ-aminobutyric acid

Abstract

It has been experimentally established that the original new generation anticonvulsant Galodif, N-[(3-chlorophenyl)-(phenyl)methyl]urea, allosterically modulates GABAA receptor (GABAAR). Binding of [3H]flunitrazepam and [3H]Ro5-4864 to the benzodiazepine (BZD) site of GABAAR in the brain of Galodif-treated rats showes an increase in receptor affinity in Scatchard Plot for Ligand Receptor binding analysis. The results of molecular docking (Schrodinger program Glide) reveal that the enantiomers of Galodif are complementary to the BZD binding site of GABAAR; binding energy of R-Galodif is lower than that of S-Galodif (scoring GScore being -11.14 and -10.7 kcal mol-1, respectively); R-Galodif interacts with key amino acids at the α1γ2 interface: Tyr159, Tyr209, H101 Phe77 with high model fit - dG of insert: 7.41.

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