Synthesis of 4-Aminopyrazol-5-ols as Edaravone Analogs and Their Antioxidant Activity
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
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Synthesis of 4-Aminopyrazol-5-ols as Edaravone Analogs and Their Antioxidant Activity
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| Автор |
Burgart, Y. V.
Makhaeva, G. F. Krasnykh, O. P. Borisevich, S. S. Agafonova, N. A. Kovaleva, N. V. Boltneva, N. P. Rudakova, E. V. Shchegolkov, E. V. Triandafilova, G. A. Gazizov, D. A. Serebryakova, O. G. Ulitko, M. V. Khursan, S. L. Saloutin, V. I. Richardson, R. J. |
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| Тематика |
4-AMINOPYRAZOL-5-OLS
4-HYDROXYIMINOPYRAZOL-5-ONES ANTIOXIDANTS ANTIRADICAL AND FERRIC REDUCING ACTIVITY EDARAVONE QUANTUM-CHEMICAL CALCULATIONS ANTIOXIDANTS CHOLINESTERASE INHIBITORS EDARAVONE HUMANS 2,2'-AZINO-DI-(3-ETHYLBENZOTHIAZOLINE)-6-SULFONIC ACID ANTIOXIDANT CHOLINESTERASE INHIBITOR NORPHENAZONE CHEMISTRY HUMAN |
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| Описание |
One of the powerful antioxidants used clinically is Edaravone (EDA). We synthesized a series of new EDA analogs, 4-aminopyrazol-5-ol hydrochlorides, including polyfluoroalkyl derivatives, via the reduction of 4-hydroxyiminopyrazol-5-ones. The primary antioxidant activity of the compounds in comparison with EDA was investigated in vitro using ABTS, FRAP, and ORAC tests. In all tests, 4-Amino-3-pyrazol-5-ols were effective. The lead compound, 4-amino-3-methyl-1-phenylpyrazol-5-ol hydrochloride (APH), showed the following activities: ABTS, 0.93 TEAC; FRAP, 0.98 TE; and ORAC, 4.39 TE. APH and its NH-analog were not cytotoxic against cultured normal human fibroblasts even at 100 μM, in contrast to EDA. According to QM calculations, 4-aminopyrazolols were characterized by lower gaps, IP, and η compared to 4-hydroxyiminopyrazol-5-ones, consistent with their higher antioxidant activities in ABTS and FRAP tests, realized by the SET mechanism. The radical-scavenging action evaluated in the ORAC test occurred by the HAT mechanism through OH bond breaking in all compounds, directly dependent on the dissociation energy of the OH bond. All the studied compounds demonstrated the absence of anticholinesterase activity and moderate inhibition of CES by some 4-aminopyrazolols. Thus, the lead compound APH was found to be a good antioxidant with the potential to be developed as a novel therapeutic drug candidate in the treatment of diseases associated with oxidative stress. © 2022 by the authors.
Ministry of Education and Science of the Russian Federation, Minobrnauka, (075-15-2020-777) This work was supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2020-777). |
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| Дата |
2024-04-08T11:06:39Z
2024-04-08T11:06:39Z 2022 |
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Article
Journal article (info:eu-repo/semantics/article) Published version (info:eu-repo/semantics/publishedVersion) |
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| Идентификатор |
Burgart, YV, Makhaeva, GF, Krasnykh, OP, Borisevich, SS, Agafonova, NA, Kovaleva, NV, Boltneva, NP, Rudakova, EV, Shchegolkov, EV, Triandafilova, GA, Gazizov, DA, Serebryakova, OG, Ulitko, MV, Khursan, SL, Saloutin, VI & Richardson, RJ 2022, 'Synthesis of 4-Aminopyrazol-5-ols as Edaravone Analogs and Their Antioxidant Activity', Molecules, Том. 27, № 22, 7722. https://doi.org/10.3390/molecules27227722
Burgart, Y. V., Makhaeva, G. F., Krasnykh, O. P., Borisevich, S. S., Agafonova, N. A., Kovaleva, N. V., Boltneva, N. P., Rudakova, E. V., Shchegolkov, E. V., Triandafilova, G. A., Gazizov, D. A., Serebryakova, O. G., Ulitko, M. V., Khursan, S. L., Saloutin, V. I., & Richardson, R. J. (2022). Synthesis of 4-Aminopyrazol-5-ols as Edaravone Analogs and Their Antioxidant Activity. Molecules, 27(22), [7722]. https://doi.org/10.3390/molecules27227722 1420-3049 Final All Open Access; Gold Open Access; Green Open Access https://www.mdpi.com/1420-3049/27/22/7722/pdf?version=1668585197 https://www.mdpi.com/1420-3049/27/22/7722/pdf?version=1668585197 http://elar.urfu.ru/handle/10995/131329 10.3390/molecules27227722 85142659494 000887551600001 |
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en
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Open access (info:eu-repo/semantics/openAccess)
cc-by https://creativecommons.org/licenses/by/4.0/ |
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application/pdf
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MDPI
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Molecules
Molecules |
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