ПРОГНОЗУВАННЯ IN SILICO БІОЛОГІЧНОЇ АКТИВНОСТІ ТА МОЛЕКУЛЯРНИЙ ДОКІНГ ПОХІДНИХ ГІДРОАКРИДИНІВ (ХІНОЛІНІВ)
To find biological activity among easily available 2-[(4S,4’S/4R,4’R)-2’,5’-dioxo-2,3,5,6,7,8-hexahydro-1H-spiro[acridine-4,3’-pyrrolidin]-4’-yl]-N-aryl-acetamide, (4S/4R)-4-[(3R/3S)-1-(2-aryl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile, (3S/4R)-3-[(3R/4S)-9-chloroacr...
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| Date: | 2021 |
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| Main Authors: | , , , , |
| Format: | Article |
| Language: | English |
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V.I.Vernadsky Institute of General and Inorganic Chemistry
2021
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| Online Access: | https://ucj.org.ua/index.php/journal/article/view/312 |
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| Journal Title: | Ukrainian Chemistry Journal |
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Ukrainian Chemistry Journal| _version_ | 1856543770372210688 |
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| author | Smetanin , Nikolay Tokarieva, Sofia Varenichenko , Svetlana Farat , Oleg Markov, Victor |
| author_facet | Smetanin , Nikolay Tokarieva, Sofia Varenichenko , Svetlana Farat , Oleg Markov, Victor |
| author_sort | Smetanin , Nikolay |
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| collection | OJS |
| datestamp_date | 2021-08-02T08:57:29Z |
| description | To find biological activity among easily available 2-[(4S,4’S/4R,4’R)-2’,5’-dioxo-2,3,5,6,7,8-hexahydro-1H-spiro[acridine-4,3’-pyrrolidin]-4’-yl]-N-aryl-acetamide, (4S/4R)-4-[(3R/3S)-1-(2-aryl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile, (3S/4R)-3-[(3R/4S)-9-chloroacridine(quinoline)-4-yl]-1-N-aryl)pyrrolidine-2,5-diones. Methods: Organic synthesis, spectral methods, and molecular docking. We investigated by molecular docking the potential biological activity of previously synthesized compounds containing acridine and pyrrolidine-2,5-diones fragments in their structure, as well as synthesized in this work N’-hydroxy-1,2,3,4,5,6,7,8-octahydroacridine-4-carboximidamide. Based on the literature data, 3 directions of searching for the biological activity of the synthesized compounds have been chosen: cholinesterase inhibitors, anti-inflammatory, and anticonvulsant agents. As inhibitors of acetylcholinesterase and butylcholinesterase, substances with good binding free energy and hydrogen bonds with the desired amino acid residues of the Glu-His-Ser triad have been found among the tested compounds. The indicators of synthesized products have exceeded the literature data. The docking data for anti-inflammatory activity has revealed compounds with values above the docking data of the reference drugs - celecoxib and indomethacin. The compounds tested have shown moderate activity as anticonvulsant agents. 3-(7-bromo-9-chloro-1,2,3,4-tetrahydroacridin-4-yl)-1-(3-nitrophenyl)pyrrolidine-2,5-dione is potentially promising as an acetylcholinesterase inhibitor due to its high binding free energy (-13.7 kcal/mol) and hydrogen bonds with two amino acid residues Ser200, His440. Compound (4S/4R)-4-[(3R/3S)-1-(3-nitrophenyl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile has proved to be the best as an anti-inflammatory agent. The presence of a pyrrolidine-2,5-diones fragment increases the indicators of the biological activity of the synthesized compounds in comparison with just acridine derivatives. |
| first_indexed | 2025-09-24T17:43:39Z |
| format | Article |
| id | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-312 |
| institution | Ukrainian Chemistry Journal |
| language | English |
| last_indexed | 2025-09-24T17:43:39Z |
| publishDate | 2021 |
| publisher | V.I.Vernadsky Institute of General and Inorganic Chemistry |
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| spelling | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-3122021-08-02T08:57:29Z IN SILICO PREDICTION AND MOLECULAR DOCKING STUDIES OF BIOLOGICAL ACTIVITY OF HYDROACRIDINE (QUINOLINE) DERIVATIVES ПРОГНОЗУВАННЯ IN SILICO БІОЛОГІЧНОЇ АКТИВНОСТІ ТА МОЛЕКУЛЯРНИЙ ДОКІНГ ПОХІДНИХ ГІДРОАКРИДИНІВ (ХІНОЛІНІВ) Smetanin , Nikolay Tokarieva, Sofia Varenichenko , Svetlana Farat , Oleg Markov, Victor 9-chloroacridine(quinoline)-N-aryl)pyrrolidine-2,5-diones, docking studies, cholinesterase inhibitors, anti-inflammatory activity, anticonvulsant activity. To find biological activity among easily available 2-[(4S,4’S/4R,4’R)-2’,5’-dioxo-2,3,5,6,7,8-hexahydro-1H-spiro[acridine-4,3’-pyrrolidin]-4’-yl]-N-aryl-acetamide, (4S/4R)-4-[(3R/3S)-1-(2-aryl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile, (3S/4R)-3-[(3R/4S)-9-chloroacridine(quinoline)-4-yl]-1-N-aryl)pyrrolidine-2,5-diones. Methods: Organic synthesis, spectral methods, and molecular docking. We investigated by molecular docking the potential biological activity of previously synthesized compounds containing acridine and pyrrolidine-2,5-diones fragments in their structure, as well as synthesized in this work N’-hydroxy-1,2,3,4,5,6,7,8-octahydroacridine-4-carboximidamide. Based on the literature data, 3 directions of searching for the biological activity of the synthesized compounds have been chosen: cholinesterase inhibitors, anti-inflammatory, and anticonvulsant agents. As inhibitors of acetylcholinesterase and butylcholinesterase, substances with good binding free energy and hydrogen bonds with the desired amino acid residues of the Glu-His-Ser triad have been found among the tested compounds. The indicators of synthesized products have exceeded the literature data. The docking data for anti-inflammatory activity has revealed compounds with values above the docking data of the reference drugs - celecoxib and indomethacin. The compounds tested have shown moderate activity as anticonvulsant agents. 3-(7-bromo-9-chloro-1,2,3,4-tetrahydroacridin-4-yl)-1-(3-nitrophenyl)pyrrolidine-2,5-dione is potentially promising as an acetylcholinesterase inhibitor due to its high binding free energy (-13.7 kcal/mol) and hydrogen bonds with two amino acid residues Ser200, His440. Compound (4S/4R)-4-[(3R/3S)-1-(3-nitrophenyl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile has proved to be the best as an anti-inflammatory agent. The presence of a pyrrolidine-2,5-diones fragment increases the indicators of the biological activity of the synthesized compounds in comparison with just acridine derivatives. V.I.Vernadsky Institute of General and Inorganic Chemistry 2021-06-25 Article Article Organic chemistry Органическая xимия Органічна xімія application/pdf https://ucj.org.ua/index.php/journal/article/view/312 10.33609/2708-129X.87.05.2021.38-52 Ukrainian Chemistry Journal; Vol. 87 No. 5 (2021): Ukrainian Chemistry Journal; 38-52 Украинский химический журнал; Том 87 № 5 (2021): Ukrainian Chemistry Journal; 38-52 Український хімічний журнал; Том 87 № 5 (2021): Український хімічний журнал; 38-52 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/312/171 |
| spellingShingle | Smetanin , Nikolay Tokarieva, Sofia Varenichenko , Svetlana Farat , Oleg Markov, Victor ПРОГНОЗУВАННЯ IN SILICO БІОЛОГІЧНОЇ АКТИВНОСТІ ТА МОЛЕКУЛЯРНИЙ ДОКІНГ ПОХІДНИХ ГІДРОАКРИДИНІВ (ХІНОЛІНІВ) |
| title | ПРОГНОЗУВАННЯ IN SILICO БІОЛОГІЧНОЇ АКТИВНОСТІ ТА МОЛЕКУЛЯРНИЙ ДОКІНГ ПОХІДНИХ ГІДРОАКРИДИНІВ (ХІНОЛІНІВ) |
| title_alt | IN SILICO PREDICTION AND MOLECULAR DOCKING STUDIES OF BIOLOGICAL ACTIVITY OF HYDROACRIDINE (QUINOLINE) DERIVATIVES |
| title_full | ПРОГНОЗУВАННЯ IN SILICO БІОЛОГІЧНОЇ АКТИВНОСТІ ТА МОЛЕКУЛЯРНИЙ ДОКІНГ ПОХІДНИХ ГІДРОАКРИДИНІВ (ХІНОЛІНІВ) |
| title_fullStr | ПРОГНОЗУВАННЯ IN SILICO БІОЛОГІЧНОЇ АКТИВНОСТІ ТА МОЛЕКУЛЯРНИЙ ДОКІНГ ПОХІДНИХ ГІДРОАКРИДИНІВ (ХІНОЛІНІВ) |
| title_full_unstemmed | ПРОГНОЗУВАННЯ IN SILICO БІОЛОГІЧНОЇ АКТИВНОСТІ ТА МОЛЕКУЛЯРНИЙ ДОКІНГ ПОХІДНИХ ГІДРОАКРИДИНІВ (ХІНОЛІНІВ) |
| title_short | ПРОГНОЗУВАННЯ IN SILICO БІОЛОГІЧНОЇ АКТИВНОСТІ ТА МОЛЕКУЛЯРНИЙ ДОКІНГ ПОХІДНИХ ГІДРОАКРИДИНІВ (ХІНОЛІНІВ) |
| title_sort | прогнозування in silico біологічної активності та молекулярний докінг похідних гідроакридинів (хінолінів) |
| topic_facet | 9-chloroacridine(quinoline)-N-aryl)pyrrolidine-2,5-diones docking studies cholinesterase inhibitors anti-inflammatory activity anticonvulsant activity. |
| url | https://ucj.org.ua/index.php/journal/article/view/312 |
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