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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 |
Файлы этого ресурса:
Файл | Описание | Размер | Формат | |
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Synthesis, docking study, and pharmacological evaluation of S-acetamide derivatives of 4,6-dimethyl-2-thiopyrimidine as anticonvulsant agents.pdf | 623,8 kB | Adobe PDF | Просмотреть/Открыть |
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