N'-isonicotinoylpicolinohydrazonamide: Synthesis, crystal structure, DFT and ADMET studies, and in silico inhibition properties toward a series of COVID-19 proteins
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
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N'-isonicotinoylpicolinohydrazonamide: Synthesis, crystal structure, DFT and ADMET studies, and in silico inhibition properties toward a series of COVID-19 proteins
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| Автор |
Garcia-Santos, I.
Castiñeiras, A. Eftekhari, Sis, B. Mahmoudi, G. Safin, D. A. |
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| Тематика |
COVID-19
CRYSTAL STRUCTURE DFT HIRSHFELD SURFACE ANALYSIS ISONIAZID ATOMS BINDING ENERGY BIOSYNTHESIS COMPLEXATION CRYSTAL ATOMIC STRUCTURE HYDRAZINE HYDROGEN BONDS MOLECULAR DYNAMICS MOLECULAR MODELING NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY PROTEINS SINGLE CRYSTALS SURFACE ANALYSIS COMPUTATIONAL ANALYSIS CRYSTAL PACKINGS CRYSTALS STRUCTURES DFT H NMR SPECTROSCOPY HIRSHFELD SURFACE ANALYSE HIRSHFELD SURFACES IN-SILICO INHIBITION PROPERTY ISONIAZID COVID-19 |
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| Описание |
In this work, synthesis as well as detailed structural and computational analyses of the novel isoniazid derivative, namely N'-isonicotinoylpicolinohydrazonamide (1), are reported. The obtained compound was examined by microanalysis, IR, 1H NMR spectroscopy and single crystal X-ray diffraction. The crystal packing was studied by the Hirshfeld surface analysis. Molecules in the crystal structure of 1 are linked through N–H⋯O and N–H⋯N hydrogen bonds, and π⋯π interactions, yielding a 1D supramolecular chain. According to the Hirshfeld surface analysis, crystal packing of 1 is primarily dictated by H⋯H, H⋯C, H⋯N and H⋯O contacts, of which the latter three contacts are highly favoured. The crystal packing is further characterized by highly favoured C⋯C contacts. Compound 1 was also studied using DFT in gas phase, which revealed its pronounced electrophilic features. The most electron-rich (nucleophilic) sites were revealed for the carbonyl oxygen atom, and 4-pyridyl and imine nitrogen atoms, while the most electron-deficient (electrophilic) sites were found for the NH and NH2 hydrogen atoms. Compound 1 was predicted to belong to a fourth class of toxicity and exhibits negative blood–brain barrier penetration and positive gastrointestinal absorption property. In silico molecular docking was applied to probe 1 as a potential inhibitor of a series of the SARS-CoV-2 proteins and it was found that 1 is potentially active against all the applied proteins with the best activity against Nonstructural protein 3 (Nsp3_range 207–379-MES). It was also established that the best docking scores for 1 were found for the cavities, where initial ligands were located, except for the Papain-like protease (PLpro). The best binding affinity of the latter protein with 1 was revealed for the other cavity with about 0.8 kcal/mol being more efficient. Molecular dynamics simulations were also applied to evaluate the stability of complexes PLproI–1, PLproII–1 and Nsp_range 207–379-MES–1. Complex PLproI–1 was found to be highly unstable, while complexes PLproII–1 and Nsp_range 207–379-MES–1 are stable. © 2023 Elsevier Ltd
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| Дата |
2024-04-05T16:17:19Z
2024-04-05T16:17:19Z 2023 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/publishedVersion |
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| Идентификатор |
Garcia-Santos, I, Castineiras, A, Eftekhari Sis, B, Mahmoudi, G & Safin, DA 2023, 'N'-isonicotinoylpicolinohydrazonamide: Synthesis, crystal structure, DFT and ADMET studies, and in silico inhibition properties toward a series of COVID-19 proteins', Polyhedron, № 235, 116362. https://doi.org/10.1016/j.poly.2023.116362
Garcia-Santos, I., Castineiras, A., Eftekhari Sis, B., Mahmoudi, G., & Safin, D. A. (2023). N'-isonicotinoylpicolinohydrazonamide: Synthesis, crystal structure, DFT and ADMET studies, and in silico inhibition properties toward a series of COVID-19 proteins. Polyhedron, (235), [116362]. https://doi.org/10.1016/j.poly.2023.116362 0277-5387 Final All Open Access, Bronze https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149747613&doi=10.1016%2fj.poly.2023.116362&partnerID=40&md5=34b2b266c2f134cbb5c526732a25eb9f https://doi.org/10.1016/j.poly.2023.116362 http://elar.urfu.ru/handle/10995/130265 10.1016/j.poly.2023.116362 85149747613 000962507700001 |
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| Язык |
en
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| Права |
Open access (info:eu-repo/semantics/openAccess)
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application/pdf
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| Издатель |
Elsevier Ltd
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| Источник |
Polyhedron
Polyhedron |
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