Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
| Заглавие |
Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury
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| Автор |
Spasov, A.
Ovchinnikova, I. Fedorova, O. Titova, Y. Babkov, D. Kosolapov, V. Borisov, A. Sokolova, E. Klochkov, V. Skripka, M. Velikorodnaya, Y. Smirnov, A. Rusinov, G. Charushin, V. |
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| Тематика |
CYTOKINE RELEASE
INFLAMMATION LUNG INJURY PYRIMIDINES [1,2,4]TRIAZOLO[1,5-A]PYRIMIDINES INTERLEUKIN 6 LIPOPOLYSACCHARIDE PROTECTIVE AGENT PYRIMIDINE DERIVATIVE ACUTE LUNG INJURY ANIMAL CHEMISTRY LUNG MOUSE ACUTE LUNG INJURY ANIMALS INTERLEUKIN-6 LIPOPOLYSACCHARIDES LUNG MICE PROTECTIVE AGENTS PYRIMIDINES |
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| Описание |
The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO. The anti-inflammatory activity of 14 target compounds was studied on isolated primary murine macrophages after LPS stimulation. Seven compounds were identified to inhibit the synthesis of nitric oxide and interleukin 6 at a concentration of 100 µM. The most active compounds are micromolar inhibitors of IL-6 secretion and NO synthesis, showing a minimal impact on innate immunity, unlike the reference drug dexamethasone, along with acceptable cytotoxicity. Evaluation in an animal model of acute lung injury proved the protective activity of compound 6e, which was supported by biochemical, cytological and morphological markers. © 2023 by the authors.
Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2020-777 This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Agreement on the provision of grants from the federal budget in the form of subsidies under paragraph 4 of Article 78.1 of the Budget Code of the Russian Federation, Moscow, 1 October 2020 No. 075-15-2020-777). |
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| Дата |
2024-04-05T16:34:33Z
2024-04-05T16:34:33Z 2023 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/publishedVersion |
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| Идентификатор |
Spasov, A, Ovchinnikova, I, Fedorova, OV, Titova, Y, Babkov, D, Kosolapov, V, Borisov, A, Sokolova, E, Klochkov, V, Skripka, M, Velikorodnaya, Y, Smirnov, A, Rusinov, G & Charushin, V 2023, 'Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury', Molecules, Том. 28, № 2, 741. https://doi.org/10.3390/molecules28020741
Spasov, A., Ovchinnikova, I., Fedorova, O. V., Titova, Y., Babkov, D., Kosolapov, V., Borisov, A., Sokolova, E., Klochkov, V., Skripka, M., Velikorodnaya, Y., Smirnov, A., Rusinov, G., & Charushin, V. (2023). Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury. Molecules, 28(2), [741]. https://doi.org/10.3390/molecules28020741 1420-3049 Final All Open Access, Gold, Green https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146661927&doi=10.3390%2fmolecules28020741&partnerID=40&md5=70b72ca2016b949c44f0ccc9a7e1a1de https://www.mdpi.com/1420-3049/28/2/741/pdf?version=1674033724 http://elar.urfu.ru/handle/10995/130859 10.3390/molecules28020741 85146661927 000918798700001 |
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| Язык |
en
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| Права |
Open access (info:eu-repo/semantics/openAccess)
cc-by https://creativecommons.org/licenses/by/4.0/ |
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| Формат |
application/pdf
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| Издатель |
MDPI
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| Источник |
Molecules
Molecules |
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