Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
| Заглавие |
Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals
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| Автор |
Burgart, Y. V.
Elkina, N. A. Shchegolkov, E. V. Krasnykh, O. P. Makhaeva, G. F. Triandafilova, G. A. Solodnikov, S. Y. Boltneva, N. P. Rudakova, E. V. Kovaleva, N. V. Serebryakova, O. G. Ulitko, M. V. Borisevich, S. S. Gerasimova, N. A. Evstigneeva, N. P. Kozlov, S. A. Korolkova, Y. V. Minin, A. S. Belousova, A. V. Mozhaitsev, E. S. Klabukov, A. M. Saloutin, V. I. |
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| Тематика |
4-ARYLHYDRAZINYLIDENEPYRAZOL-3-ONES
ADME PROFILE ANTIMICROBIAL ACTIVITY ANTINOCICEPTIVE EFFECT ANTIOXIDANT ACTIVITY CARBOXYLESTERASE INHIBITOR CYTOTOXICITY TRPV1 RECEPTOR INHIBITOR ANTIOXIDANT DICLOFENAC DRUG CHEMISTRY HUMAN MOLECULAR DOCKING ANTIOXIDANTS DICLOFENAC HUMANS MOLECULAR DOCKING SIMULATION PHARMACEUTICAL PREPARATIONS |
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| Описание |
4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were found to be obtained by the regiospecific cyclization of 2-arylhydrazinylidene-3-(polyfluoroalkyl)-3-oxoesters with hydrazines, by the azo coupling of 4-nonsubstituted pyrazol-5-oles with aryldiazonium chlorides or by the firstly discovered acid-promoted self-condensation of 2-arylhydrazinylidene-3-oxoesters. All the 4-AHPs had an acceptable ADME profile. Varying the substituents in 4-AHPs promoted the switching or combining of their biological activity. The polyfluoroalkyl residue in 4-AHPs led to the appearance of an anticarboxylesterase action in the micromolar range. An NH-fragment and/or methyl group instead of the polyfluoroalkyl one in the 4-AHPs promoted antioxidant properties in the ABTS, FRAP and ORAC tests, as well as anti-cancer activity against HeLa that was at the Doxorubicin level coupled with lower cytotoxicity against normal human fibroblasts. Some Ph-N-substituted 4-AHPs could inhibit the growth of N. gonorrhoeae bacteria at MIC 0.9 μg/mL. The possibility of using 4-AHPs for cell visualization was shown. Most of the 4-AHPs exhibited a pronounced analgesic effect in a hot plate test in vivo at and above the diclofenac and metamizole levels except for the ones with two chlorine atoms in the aryl group. The methylsulfonyl residue was proved to raise the anti-inflammatory effect also. A mechanism of the antinociceptive action of the 4-AHPs through blocking the TRPV1 receptor was proposed and confirmed using in vitro experiment and molecular docking. © 2022 by the authors.
FFSN-2021-0005; Russian Foundation for Basic Research, РФФИ: 20-03-00312; Russian Science Foundation, RSF: 21-13-00390 This work was financially supported by the Russian Science Foundation (grant No 21-13-00390 for V.I.S.): the synthesis and analysis of compounds, antimicrobial evaluation, cytotoxicity, analgesic and anti-inflammatory activity, mechanism of analgesia, molecular docking; by the Russian Foundation for Basic Research (grant No 20-03-00312 for Y.V.B.): esterase profile of compounds; antioxidant activity in ABTS and FRAP tests were performed in the frame of IPAC RAS State Targets Project FFSN-2021-0005. |
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| Дата |
2024-04-05T16:22:44Z
2024-04-05T16:22:44Z 2023 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/publishedVersion |
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| Идентификатор |
Burgart, YV, Elkina, NA, Shchegolkov, EV, Krasnykh, OP, Makhaeva, GF, Triandafilova, GA, Solodnikov, SY, Boltneva, NP, Rudakova, EV, Kovaleva, NV, Serebryakova, OG, Ulitko, MV, Borisevich, SS, Gerasimova, NA, Evstigneeva, NP, Kozlov, SA, Korolkova, YV, Minin, AS, Belousova, AV, Mozhaitsev, ES, Klabukov, AM & Saloutin, VI 2023, 'Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals', Molecules, Том. 28, № 1, 59. https://doi.org/10.3390/molecules28010059
Burgart, Y. V., Elkina, N. A., Shchegolkov, E. V., Krasnykh, O. P., Makhaeva, G. F., Triandafilova, G. A., Solodnikov, S. Y., Boltneva, N. P., Rudakova, E. V., Kovaleva, N. V., Serebryakova, O. G., Ulitko, M. V., Borisevich, S. S., Gerasimova, N. A., Evstigneeva, N. P., Kozlov, S. A., Korolkova, Y. V., Minin, A. S., Belousova, A. V., ... Saloutin, V. I. (2023). Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals. Molecules, 28(1), [59]. https://doi.org/10.3390/molecules28010059 1420-3049 Final All Open Access, Gold, Green https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145721993&doi=10.3390%2fmolecules28010059&partnerID=40&md5=40abed089c93b2d2117287a0bae505d0 https://www.mdpi.com/1420-3049/28/1/59/pdf?version=1672046166 http://elar.urfu.ru/handle/10995/130503 10.3390/molecules28010059 85145721993 000910041900001 |
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| Язык |
en
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| Связанные ресурсы |
info:eu-repo/grantAgreement/RSF//21-13-00390
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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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