Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
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Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay
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| Автор |
Nikiforov, E. A.
Vaskina, N. F. Moseev, T. D. Varaksin, M. V. Butorin, I. I. Melekhin, V. V. Tokhtueva, M. D. Mazhukin, D. G. Tikhonov, A. Y. Charushin, V. N. Chupakhin, O. N. |
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| Тематика |
AZAHETEROCYCLES
C-H FUNCTIONALIZATION IMIDAZOLES IN VITRO CYTOTOXICITY ASSAY INDOLES MOLECULAR DOCKING NEURODEGENERATIVE DISEASES NUCLEOPHILIC SUBSTITUTION OF HYDROGEN PASE |
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| Описание |
The strategy of the nucleophilic substitution of hydrogen (SNH) was first applied for the metal-free C-H/C-H coupling reactions of 4H-imidazole 3-oxides with indoles. As a result, a series of novel bifunctional azaheterocyclic derivatives were obtained in yields up to 95%. In silico experiments on the molecular docking were performed to evaluate the binding possibility of the synthesized small azaheterocyclic molecules to the selected biotargets (BACE1, BChE, CK1δ, AChE) associated with the pathogenesis of neurodegenerative diseases. To assess the cytotoxicity for the synthesized compounds, a series of in vitro experiments were also carried out on healthy human embryo kidney cells (HEK-293). The leading compound bearing both 5-phenyl-4H-imidazole and 1-methyl-1H-indole moieties was defined as the prospective molecule possessing the lowest cytotoxicity (IC50 > 300 µM on HEK-293) and the highest binding energy in the protein–ligand complex (AChE, −13.57 kcal/mol). The developed compounds could be of particular interest in medicinal chemistry, particularly in the targeted design of small-molecule candidates for the treatment of neurodegenerative disorders. © 2023 by the authors.
Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2022-1118, W03.31.0034; Russian Science Foundation, RSF: 20-73-10077 The chemical design, synthesis and characterization of indolyl-derived 4H -imidazoles and in vitro studies were supported by the Russian Science Foundation (Project # 20-73-10077). The in silico studies were supported by the Ministry of Science and Higher Education of the Russian Federation (Ref. # 075-15-2022-1118, dated 29 June 2022). The synthesis of starting 4H -imidazole N -oxide substrates was supported by the Ministry of Science and Higher Education of the Russian Federation (Project # 14.W03.31.0034). |
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| Дата |
2024-04-05T16:19:00Z
2024-04-05T16:19:00Z 2023 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/publishedVersion |
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| Идентификатор |
Nikiforov, EA, Vaskina, NF, Moseev, TD, Varaksin, MV, Butorin, II, Melekhin, VV, Tokhtueva, MD, Mazhukin, DG, Tikhonov, AY, Charushin, VN & Chupakhin, ON 2023, 'Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay', Processes, Том. 11, № 3, 846. https://doi.org/10.3390/pr11030846
Nikiforov, E. A., Vaskina, N. F., Moseev, T. D., Varaksin, M. V., Butorin, I. I., Melekhin, V. V., Tokhtueva, M. D., Mazhukin, D. G., Tikhonov, A. Y., Charushin, V. N., & Chupakhin, O. N. (2023). Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay. Processes, 11(3), [846]. https://doi.org/10.3390/pr11030846 2227-9717 Final All Open Access, Gold, Green https://www.scopus.com/inward/record.uri?eid=2-s2.0-85151628875&doi=10.3390%2fpr11030846&partnerID=40&md5=c0b1c53ea9cb67b9799002ad7d0bdb8e https://www.mdpi.com/2227-9717/11/3/846/pdf?version=1679366345 http://elar.urfu.ru/handle/10995/130368 10.3390/pr11030846 85151628875 000958762900001 |
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| Язык |
en
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| Связанные ресурсы |
info:eu-repo/grantAgreement/RSF//20-73-10077
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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 |
Processes
Processes |
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