Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising ­anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies

In this study, a library of phthalimide Schiff base linked to 1,4-disubstituted-1,2,3-triazoles was designed, synthesised, and characterised by different spectral analyses. All analogues have been introduced for in vitro assay of their antiviral activity against COVID-19 virus using Vero cell as inc...

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Main Authors: Ateyatallah Aljuhani, Mosa Alsehli, Mohamed A. Seleem, Shaya Y. Alraqa, Hany E. A. Ahmed, Nadjet Rezki, Mohamed R. Aouad
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
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Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2024.2351861
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author Ateyatallah Aljuhani
Mosa Alsehli
Mohamed A. Seleem
Shaya Y. Alraqa
Hany E. A. Ahmed
Nadjet Rezki
Mohamed R. Aouad
author_facet Ateyatallah Aljuhani
Mosa Alsehli
Mohamed A. Seleem
Shaya Y. Alraqa
Hany E. A. Ahmed
Nadjet Rezki
Mohamed R. Aouad
author_sort Ateyatallah Aljuhani
collection DOAJ
description In this study, a library of phthalimide Schiff base linked to 1,4-disubstituted-1,2,3-triazoles was designed, synthesised, and characterised by different spectral analyses. All analogues have been introduced for in vitro assay of their antiviral activity against COVID-19 virus using Vero cell as incubator with different concentrations. The data revealed most of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with no or weak cytotoxic effect on Vero cells. Furthermore, in vitro assay was done against this enzyme for all analogues and the results showed two of them have IC50 data by 90 µM inhibitory activity. An extensive molecular docking simulation was run to analyse their antiviral mechanism that found the proper non-covalent interaction within the Mpro protease enzyme. Finally, we profiled two reversible inhibitors, COOH and F substituted analogues that might be promising drug candidates for further development have been discovered.
format Article
id doaj-art-91a3242defff4bdeac22f1092d3006ee
institution DOAJ
issn 1475-6366
1475-6374
language English
publishDate 2024-12-01
publisher Taylor & Francis Group
record_format Article
series Journal of Enzyme Inhibition and Medicinal Chemistry
spelling doaj-art-91a3242defff4bdeac22f1092d3006ee2025-08-20T02:40:33ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2351861Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising ­anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studiesAteyatallah Aljuhani0Mosa Alsehli1Mohamed A. Seleem2Shaya Y. Alraqa3Hany E. A. Ahmed4Nadjet Rezki5Mohamed R. Aouad6Chemistry Department, College of Sciences, Taibah University, Saudi ArabiaChemistry Department, College of Sciences, Taibah University, Saudi ArabiaPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr, City, Cairo, EgyptChemistry Department, College of Sciences, Taibah University, Saudi ArabiaPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr, City, Cairo, EgyptChemistry Department, College of Sciences, Taibah University, Saudi ArabiaChemistry Department, College of Sciences, Taibah University, Saudi ArabiaIn this study, a library of phthalimide Schiff base linked to 1,4-disubstituted-1,2,3-triazoles was designed, synthesised, and characterised by different spectral analyses. All analogues have been introduced for in vitro assay of their antiviral activity against COVID-19 virus using Vero cell as incubator with different concentrations. The data revealed most of these derivatives showed potent cellular anti-COVID-19 activity and prevent viral growth by more than 90% at two different concentrations with no or weak cytotoxic effect on Vero cells. Furthermore, in vitro assay was done against this enzyme for all analogues and the results showed two of them have IC50 data by 90 µM inhibitory activity. An extensive molecular docking simulation was run to analyse their antiviral mechanism that found the proper non-covalent interaction within the Mpro protease enzyme. Finally, we profiled two reversible inhibitors, COOH and F substituted analogues that might be promising drug candidates for further development have been discovered.https://www.tandfonline.com/doi/10.1080/14756366.2024.2351861123-TriazolephtalamideSchiff basesCOVID-19molecular docking
spellingShingle Ateyatallah Aljuhani
Mosa Alsehli
Mohamed A. Seleem
Shaya Y. Alraqa
Hany E. A. Ahmed
Nadjet Rezki
Mohamed R. Aouad
Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising ­anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies
Journal of Enzyme Inhibition and Medicinal Chemistry
123-Triazole
phtalamide
Schiff bases
COVID-19
molecular docking
title Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising ­anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies
title_full Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising ­anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies
title_fullStr Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising ­anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies
title_full_unstemmed Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising ­anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies
title_short Exploring of N-phthalimide-linked 1,2,3-triazole analogues with promising ­anti-SARS-CoV-2 activity: synthesis, biological screening, and molecular modelling studies
title_sort exploring of n phthalimide linked 1 2 3 triazole analogues with promising anti sars cov 2 activity synthesis biological screening and molecular modelling studies
topic 123-Triazole
phtalamide
Schiff bases
COVID-19
molecular docking
url https://www.tandfonline.com/doi/10.1080/14756366.2024.2351861
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