دورية أكاديمية
Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury
| العنوان: | Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury |
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| المؤلفون: | 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. |
| المصدر: | Molecules |
| بيانات النشر: | MDPI |
| سنة النشر: | 2023 |
| المجموعة: | Ural Federal University (URFU): ELAR / Уральский федеральный университет: электронный архив УрФУ |
| مصطلحات موضوعية: | 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, ANIMALS, INTERLEUKIN-6, LIPOPOLYSACCHARIDES, MICE, PROTECTIVE AGENTS |
| الوصف: | 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). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-0-00-918798-8 0-00-918798-7 |
| تدمد: | 1420-3049 |
| العلاقة: | 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/molecules28020741Test; 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/molecules28020741Test; 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=70b72ca2016b949c44f0ccc9a7e1a1deTest; https://www.mdpi.com/1420-3049/28/2/741/pdf?version=1674033724Test; http://elar.urfu.ru/handle/10995/130859Test; 85146661927; 000918798700001 |
| DOI: | 10.3390/molecules28020741 |
| الإتاحة: | https://doi.org/10.3390/molecules28020741Test http://elar.urfu.ru/handle/10995/130859Test https://www.mdpi.com/1420-3049/28/2/741/pdf?version=1674033724Test |
| حقوق: | info:eu-repo/semantics/openAccess ; cc-by ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.A77E657F |
| قاعدة البيانات: | BASE |
Full Text Finder | ردمك: | 9780009187988 0009187987 |
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| تدمد: | 14203049 |
| DOI: | 10.3390/molecules28020741 |