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Название: Synthesis, docking study, and pharmacological evaluation of S-acetamide derivatives of 4,6-dimethyl-2-thiopyrimidine as anticonvulsant agents
Авторы: Severina, H. I.
Skupa, O. O.
Voloshchuk, N. I.
Georgiyants, V. A.
Сєвєріна, Г. І.
Скупа, О. О.
Волощук, Н. І.
Георгіянц, В. А.
Северина, А. И.
Скупая, О. О.
Волощук, Н. И.
Георгиянц, В. А.
Ключевые слова: 2-thiopyrimidine;docking;GABA;anticonvulsant activity;2-тіопіримідин;стикування;ГАМК;протисудомна активність;2-тиопиримидин;стыковка;противосудорожная активность
Дата публикации: 2020
Библиографическое описание: Synthesis, docking study, and pharmacological evaluation of S-acetamide derivatives of 4,6-dimethyl-2-thiopyrimidine as anticonvulsant agents / H. I. Severina, O. O. Skupa, N. I. Voloshchuk, V. A. Georgiyants // Journal of Applied Pharmaceutical Science. - 2020. - Vol.10, № 07. - Р. 001-008. doi : 0.7324/JAPS.2020.10701
Краткий осмотр (реферат): The aim of this study is the direct synthesis of new (4,6-dimethylpyrimidin-2-yl)thio-N-acetamides derivatives as possible anticonvulsants. The interaction of thiourea with acetylacetone in sodium ethoxide resulted in the scaffold of 4,6-dimethyl-2-thiopyrimidine. Thioacetamide derivatives were synthesized by alkylation of 4,6-dimethyl-2-thiopyrimidine with comparable α-chloroacetamides in the Dimethylformamide (DMF) environment and in the presence of К2 СО3. The methods of 1 H and 13C Nuclear magnetic resonance (NMR) spectroscopy, Liquid chromatography–mass spectrometry (LS/MS), and elemental analysis established the structure of the synthesized compounds. The affinity of the studied compounds with anticonvulsant biotargets— Type-A γ-aminobutyric acid receptor (GABAAR) and the gamma-aminobutyric acid-aminotransferase enzyme—was carried out using the molecular-docking method. The highest affinity was predicted for the compound having 4-bromophenyl substituent: −7.0 (GABAA) and −8.0 (GABAАТ) kcal/mol. Nevertheless, all the studied compounds conceded to the reference ligands—phenobarbital (−7.6 kcal/mol) and vigabatrin (−9.0 kcal/mol). The model of pentylenetetrazole-induced seizures in rats has shown that the studied compounds have moderate anticonvulsant activity. 4-Bromophenyl acetamide has also shown the most pronounced activity: the substance statistically significantly extended the latency period and reduced the duration of seizures by 3.4 and 2.2 times, respectively; moreover, it reduced lethality of the laboratory animals by 80% and by 2.5 times severity of seizures. Correspondence between the docking results and in vivo studies, using PTZ-induced seizures, as well as some parameters of “structure-anticonvulsant activity” correlation, was determined.
URI (Унифицированный идентификатор ресурса): http://dspace.nuph.edu.ua/handle/123456789/26761
Располагается в коллекциях:Наукові публікації кафедри фармацевтичної хімії



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