A Novel Ambroxol-Derived Tetrahydroquinazoline with a Potency against SARS-CoV-2 Proteins
Электронный научный архив УРФУ
Информация об архиве | Просмотр оригинала| Поле | Значение | |
| Заглавие |
A Novel Ambroxol-Derived Tetrahydroquinazoline with a Potency against SARS-CoV-2 Proteins
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| Автор |
Krysantieva, A. I.
Voronina, J. K. Safin, D. A. |
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| Тематика |
AMBROXOL
COVID-19 CRYSTAL STRUCTURE MOLECULAR DOCKING MOLECULAR DYNAMICS NMR SARS-COV-2 SYNTHESIS TETRAHYDROQUINAZOLINE X-RAY 2 [6,8 DIBROMO 3 (4 HYDROXYCYCLOHEXYL) 1,2,3,4 TETRAHYDROQUINAZOLIN 2 YL]PHENOL ALCOHOL AMBROXOL CARBON CORONAVIRUS PAPAIN-LIKE PROTEASE CORONAVIRUS PROTEIN LIGAND METHANOL NONSTRUCTURAL PROTEIN 3 SALICYLALDEHYDE TETRAHYDROQUINAZOLINE DERIVATIVE UNCLASSIFIED DRUG PAPAIN PEPTIDE HYDROLASE ARTICLE BINDING AFFINITY BLOOD BRAIN BARRIER CHIRALITY CONTROLLED STUDY CORONAVIRUS DISEASE 2019 CRYSTAL STRUCTURE DENSITY FUNCTIONAL THEORY DRUG ABSORPTION DRUG BINDING SITE DRUG BIOAVAILABILITY DRUG DISTRIBUTION DRUG EXCRETION DRUG METABOLISM DRUG POTENCY DRUG SYNTHESIS ELEMENTAL ANALYSIS GASTROINTESTINAL ABSORPTION INFRARED SPECTROSCOPY ISOMER ISOMERIZATION MOLECULAR DOCKING MOLECULAR DYNAMICS MOLECULAR STABILITY NONHUMAN NUCLEAR MAGNETIC RESONANCE PROTON NUCLEAR MAGNETIC RESONANCE RACEMIC MIXTURE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 TOXICITY TESTING ULTRAVIOLET VISIBLE SPECTROSCOPY X RAY POWDER DIFFRACTION HUMAN METABOLISM AMBROXOL COVID-19 HUMANS MOLECULAR DOCKING SIMULATION PAPAIN PEPTIDE HYDROLASES SARS-COV-2 |
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| Описание |
We report synthesis of a novel 1,2,3,4-tetrahydroquinazoline derivative, named 2-(6,8-dibromo-3-(4-hydroxycyclohexyl)-1,2,3,4-tetrahydroquinazolin-2-yl)phenol (1), which was obtained from the hydrochloride of 4-((2-amino-3,5-dibromobenzyl)amino)cyclohexan-1-ol (ambroxol hydrochloride) and salicylaldehyde in EtOH. The resulting compound was produced in the form of colorless crystals of the composition 1∙0.5EtOH. The formation of the single product was confirmed by the IR and 1H spectroscopy, single-crystal and powder X-ray diffraction, and elemental analysis. The molecule of 1 contains a chiral tertiary carbon of the 1,2,3,4-tetrahydropyrimidine fragment and the crystal structure of 1∙0.5EtOH is a racemate. Optical properties of 1∙0.5EtOH were revealed by UV-vis spectroscopy in MeOH and it was established that the compound absorbs exclusively in the UV region up to about 350 nm. 1∙0.5EtOH in MeOH exhibits dual emission and the emission spectra contains bands at about 340 and 446 nm upon excitation at 300 and 360 nm, respectively. The DFT calculations were performed to verify the structure as well as electronic and optical properties of 1. ADMET properties of the R-isomer of 1 were evaluated using the SwissADME, BOILED-Egg, and ProTox-II tools. As evidenced from the blue dot position in the BOILED-Egg plot, both human blood–brain barrier penetration and gastrointestinal absorption properties are positive with the positive PGP effect on the molecule. Molecular docking was applied to examine the influence of the structures of both R-isomer and S-isomer of 1 on a series of the SARS-CoV-2 proteins. According to the docking analysis results, both isomers of 1 were found to be active against all the applied SARS-CoV-2 proteins with the best binding affinities with Papain-like protease (PLpro) and nonstructural protein 3 (Nsp3_range 207–379-AMP). Ligand efficiency scores for both isomers of 1 inside the binding sites of the applied proteins were also revealed and compared with the initial ligands. Molecular dynamics simulations were also applied to evaluate the stability of complexes of both isomers with Papain-like protease (PLpro) and nonstructural protein 3 (Nsp3_range 207–379-AMP). The complex of the S-isomer with Papain-like protease (PLpro) was found to be highly unstable, while the other complexes are stable. © 2023 by the authors.
Ministry of Science and Higher Education of the Russian Federation This work was partially performed using resources of the Research Resource Center «Natural Resource Management and Physico–Chemical Research» (University of Tyumen). X-ray studies were conducted at the N.S. Kurnakov Institute of General and Inorganic Chemistry and were supported by the Ministry of Science and Higher Education of Russia as part of the state assignment of the Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences. |
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| Дата |
2024-04-05T16:17:28Z
2024-04-05T16:17:28Z 2023 |
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| Тип |
Article
Journal article (info:eu-repo/semantics/article) |info:eu-repo/semantics/publishedVersion |
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| Идентификатор |
Krysantieva, AI, Voronina, JK & Safin, DA 2023, 'A Novel Ambroxol-Derived Tetrahydroquinazoline with a Potency against SARS-CoV-2 Proteins', International Journal of Molecular Sciences, Том. 24, № 5, 4660. https://doi.org/10.3390/ijms24054660
Krysantieva, A. I., Voronina, J. K., & Safin, D. A. (2023). A Novel Ambroxol-Derived Tetrahydroquinazoline with a Potency against SARS-CoV-2 Proteins. International Journal of Molecular Sciences, 24(5), [4660]. https://doi.org/10.3390/ijms24054660 1661-6596 Final All Open Access, Gold, Green https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149865474&doi=10.3390%2fijms24054660&partnerID=40&md5=d393beede35287c50cfe9c01a4437c1d https://www.mdpi.com/1422-0067/24/5/4660/pdf?version=1678180496 http://elar.urfu.ru/handle/10995/130271 10.3390/ijms24054660 85149865474 |
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| Язык |
en
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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 |
Multidisciplinary Digital Publishing Institute (MDPI)
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| Источник |
International Journal of Molecular Sciences
International Journal of Molecular Sciences |
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