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A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins
Synthesis, characterization and theoretical studies of a novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1), which was fabricated from 4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazole-3-thiol and 4-(chloromethyl)-6,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer India
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845830/ https://www.ncbi.nlm.nih.gov/pubmed/36686402 http://dx.doi.org/10.1007/s12039-022-02127-0 |
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author | Omar, Rebaz Anwar Koparir, Pelin Sarac, Kamuran Koparir, Metin Safin, Damir A |
author_facet | Omar, Rebaz Anwar Koparir, Pelin Sarac, Kamuran Koparir, Metin Safin, Damir A |
author_sort | Omar, Rebaz Anwar |
collection | PubMed |
description | Synthesis, characterization and theoretical studies of a novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1), which was fabricated from 4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazole-3-thiol and 4-(chloromethyl)-6,7-dimethyl-2H-chromen-2-one, are reported. The resulting compound was characterized by microanalysis, IR, (1)H, and (13)C APT NMR spectroscopy. The DFT calculations examined the structure and electronic properties of 1 in gas phase. Its reactivity descriptors and molecular electrostatic potential revealed the reactivity and the reactive centers of 1. ADMET properties of 1 were evaluated using the respective online tools. It was established that 1 exhibit positive gastrointestinal absorption properties and negative human blood-brain barrier penetration. The Toxicity Model Report revealed that 1 belongs to toxicity class 4. Molecular docking was additionally applied to study the interaction of 1 with some SARS-CoV-2 proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with Papain-like protease (PLpro). The interaction of 1 with the applied proteins was also studied using molecular dynamics simulations. GRAPHICAL ABSTRACT: A novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1) is reported. The structure and electronic properties of 1 were examined by the DFT calculations. ADMET properties of 1 were also evaluated. Molecular docking and molecular dynamics simulations were applied to study interactions of 1 with a series of the SARS-CoV-2 proteins. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12039-022-02127-0. |
format | Online Article Text |
id | pubmed-9845830 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer India |
record_format | MEDLINE/PubMed |
spelling | pubmed-98458302023-01-18 A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins Omar, Rebaz Anwar Koparir, Pelin Sarac, Kamuran Koparir, Metin Safin, Damir A J Chem Sci (Bangalore) Regular Article Synthesis, characterization and theoretical studies of a novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1), which was fabricated from 4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazole-3-thiol and 4-(chloromethyl)-6,7-dimethyl-2H-chromen-2-one, are reported. The resulting compound was characterized by microanalysis, IR, (1)H, and (13)C APT NMR spectroscopy. The DFT calculations examined the structure and electronic properties of 1 in gas phase. Its reactivity descriptors and molecular electrostatic potential revealed the reactivity and the reactive centers of 1. ADMET properties of 1 were evaluated using the respective online tools. It was established that 1 exhibit positive gastrointestinal absorption properties and negative human blood-brain barrier penetration. The Toxicity Model Report revealed that 1 belongs to toxicity class 4. Molecular docking was additionally applied to study the interaction of 1 with some SARS-CoV-2 proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with Papain-like protease (PLpro). The interaction of 1 with the applied proteins was also studied using molecular dynamics simulations. GRAPHICAL ABSTRACT: A novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one (1) is reported. The structure and electronic properties of 1 were examined by the DFT calculations. ADMET properties of 1 were also evaluated. Molecular docking and molecular dynamics simulations were applied to study interactions of 1 with a series of the SARS-CoV-2 proteins. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12039-022-02127-0. Springer India 2023-01-18 2023 /pmc/articles/PMC9845830/ /pubmed/36686402 http://dx.doi.org/10.1007/s12039-022-02127-0 Text en © Indian Academy of Sciences 2023 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Regular Article Omar, Rebaz Anwar Koparir, Pelin Sarac, Kamuran Koparir, Metin Safin, Damir A A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins |
title | A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins |
title_full | A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins |
title_fullStr | A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins |
title_full_unstemmed | A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins |
title_short | A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins |
title_sort | novel coumarin-triazole-thiophene hybrid: synthesis, characterization, admet prediction, molecular docking and molecular dynamics studies with a series of sars-cov-2 proteins |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845830/ https://www.ncbi.nlm.nih.gov/pubmed/36686402 http://dx.doi.org/10.1007/s12039-022-02127-0 |
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