Novel [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity
This study of the interaction system of binucleophilic 3-substituted 4-amino-4<i>H</i>-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadia...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/22/7940 |
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| author | Andrey V. Khramchikhin Mariya A. Skryl’nikova Iana L. Esaulkova Ekaterina O. Sinegubova Vladimir V. Zarubaev Maxim A. Gureev Aleksandra M. Puzyk Vladimir A. Ostrovskii |
| author_facet | Andrey V. Khramchikhin Mariya A. Skryl’nikova Iana L. Esaulkova Ekaterina O. Sinegubova Vladimir V. Zarubaev Maxim A. Gureev Aleksandra M. Puzyk Vladimir A. Ostrovskii |
| author_sort | Andrey V. Khramchikhin |
| collection | DOAJ |
| description | This study of the interaction system of binucleophilic 3-substituted 4-amino-4<i>H</i>-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and 8-phenyl-[1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine. Among the 20 compounds studied in vitro against influenza A/Puerto Rico/8/34 (H1N1) virus, half of them demonstrated selectivity index (SI) of 10 or higher and one of them (4-((3-phenylprop-2-yn-1-yl)amino)-4<i>H</i>-1,2,4-triazole-3-thiol) possessed the highest (SI > 300). Docking results and values showed that the preferred interactant for our ligands was M2 proton channel of the influenza A virus. Protein-ligand interactions modeling showed that the aliphatic moiety of ligands could negatively regulate target activity level. |
| first_indexed | 2024-03-09T18:07:13Z |
| format | Article |
| id | doaj.art-a8c1e5f826574dec9a1c2d9641285a24 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:07:13Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a8c1e5f826574dec9a1c2d9641285a242023-11-24T09:23:46ZengMDPI AGMolecules1420-30492022-11-012722794010.3390/molecules27227940Novel [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation ActivityAndrey V. Khramchikhin0Mariya A. Skryl’nikova1Iana L. Esaulkova2Ekaterina O. Sinegubova3Vladimir V. Zarubaev4Maxim A. Gureev5Aleksandra M. Puzyk6Vladimir A. Ostrovskii7Department of Organic Chemistry, Saint Petersburg State Institute of Technology, Technical University, 26 Moskovsky Avenue, 190013 St. Petersburg, RussiaDepartment of Organic Chemistry, Saint Petersburg State Institute of Technology, Technical University, 26 Moskovsky Avenue, 190013 St. Petersburg, RussiaSaint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, 14 Mira Street, 197101 St. Petersburg, RussiaSaint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, 14 Mira Street, 197101 St. Petersburg, RussiaSaint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, 14 Mira Street, 197101 St. Petersburg, RussiaCenter of Bio and Cheminformatics, I. M. Sechenov First Moscow State Medical University, Trubetskaya 8/2, 119991 Moscow, RussiaResearch Park, Saint Petersburg State University, 26, Universitetskii Prospect, Petergof, 198504 St. Petersburg, RussiaDepartment of Chemistry and Technology of Organic Nitrogen Compounds, Saint Petersburg State Institute of Technology, Technical University, 26 Moskovsky Avenue, 190013 St. Petersburg, RussiaThis study of the interaction system of binucleophilic 3-substituted 4-amino-4<i>H</i>-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and 8-phenyl-[1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine. Among the 20 compounds studied in vitro against influenza A/Puerto Rico/8/34 (H1N1) virus, half of them demonstrated selectivity index (SI) of 10 or higher and one of them (4-((3-phenylprop-2-yn-1-yl)amino)-4<i>H</i>-1,2,4-triazole-3-thiol) possessed the highest (SI > 300). Docking results and values showed that the preferred interactant for our ligands was M2 proton channel of the influenza A virus. Protein-ligand interactions modeling showed that the aliphatic moiety of ligands could negatively regulate target activity level.https://www.mdpi.com/1420-3049/27/22/7940drug designannelated heterocyclesinfluenza virusanti-viral activity[1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazines[1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepines |
| spellingShingle | Andrey V. Khramchikhin Mariya A. Skryl’nikova Iana L. Esaulkova Ekaterina O. Sinegubova Vladimir V. Zarubaev Maxim A. Gureev Aleksandra M. Puzyk Vladimir A. Ostrovskii Novel [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity Molecules drug design annelated heterocycles influenza virus anti-viral activity [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazines [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepines |
| title | Novel [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity |
| title_full | Novel [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity |
| title_fullStr | Novel [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity |
| title_full_unstemmed | Novel [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity |
| title_short | Novel [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity |
| title_sort | novel 1 2 4 triazolo 3 4 i b i 1 3 4 thiadiazine and 1 2 4 triazolo 3 4 i b i 1 3 4 thiadiazepine derivatives synthesis anti viral in vitro study and target validation activity |
| topic | drug design annelated heterocycles influenza virus anti-viral activity [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazines [1,2,4]triazolo[3,4-<i>b</i>][1,3,4]thiadiazepines |
| url | https://www.mdpi.com/1420-3049/27/22/7940 |
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