T. V. Shushpanova, N. A. Bokhan, V. Yu. Kuksenok, V. V. Shtrykova, O. V. Shushpanova, V. V. Udut, “A novel urea derivative anticonvulsant: In vivo biological evaluation, radioreceptor analysis of GABAA receptors and molecular docking studies of enantiomers”, Mendeleev Commun., 33:4 (2023), 546

Эта публикация цитируется в 9 статьях

Communications

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

T. V. Shushpanova^a, N. A. Bokhan^ab, V. Yu. Kuksenok^c, V. V. Shtrykova^c, O. V. Shushpanova^d, V. V. Udut^e

^a Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation
^b Siberian State Medical University, Tomsk, Russian Federation
^c National Research Tomsk Polytechnic University, Tomsk, Russian Federation
^d Scientific Center for Mental Health, Moscow, Russian Federation
^e E.D. Goldberg Scientific Research Institute of Pharmacology and Regenerative Medicine, Tomsk Research Center, Russian Academy of Sciences, Tomsk, Russian Federation

Аннотация: It has been experimentally established that the original new generation anticonvulsant Galodif, N-[(3-chlorophenyl)-(phenyl)methyl]urea, allosterically modulates GABA_A receptor (GABA_AR). Binding of [³H]flunitrazepam and [³H]Ro5-4864 to the benzodiazepine (BZD) site of GABA_AR 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 (Schrödinger program Glide) reveal that the enantiomers of Galodif are complementary to the BZD binding site of GABA_AR; 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.

Ключевые слова: anticonvulsants, γ-aminobutyric acid, molecular docking, GABA_A receptor, enantiomers.

Язык публикации: английский

DOI: 10.1016/j.mencom.2023.06.034