Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides

[Image: see text] Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase S...

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Autores principales: Leusciatti, Marco, Macchi, Beatrice, Marino-Merlo, Francesca, Mastino, Antonio, Morra, Giulia, Quadrelli, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552509/
https://www.ncbi.nlm.nih.gov/pubmed/37810686
http://dx.doi.org/10.1021/acsomega.3c04918
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author Leusciatti, Marco
Macchi, Beatrice
Marino-Merlo, Francesca
Mastino, Antonio
Morra, Giulia
Quadrelli, Paolo
author_facet Leusciatti, Marco
Macchi, Beatrice
Marino-Merlo, Francesca
Mastino, Antonio
Morra, Giulia
Quadrelli, Paolo
author_sort Leusciatti, Marco
collection PubMed
description [Image: see text] Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase SARS-CoV-2 inhibition. The setup phosphorylation protocol afforded the nucleotides available for the biological tests. Preliminary inhibition and cytotoxicity assays were then performed, and the results showed a moderate activity of the nucleotides accompanied by cytotoxicity.
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spelling pubmed-105525092023-10-06 Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides Leusciatti, Marco Macchi, Beatrice Marino-Merlo, Francesca Mastino, Antonio Morra, Giulia Quadrelli, Paolo ACS Omega [Image: see text] Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase SARS-CoV-2 inhibition. The setup phosphorylation protocol afforded the nucleotides available for the biological tests. Preliminary inhibition and cytotoxicity assays were then performed, and the results showed a moderate activity of the nucleotides accompanied by cytotoxicity. American Chemical Society 2023-09-20 /pmc/articles/PMC10552509/ /pubmed/37810686 http://dx.doi.org/10.1021/acsomega.3c04918 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Leusciatti, Marco
Macchi, Beatrice
Marino-Merlo, Francesca
Mastino, Antonio
Morra, Giulia
Quadrelli, Paolo
Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides
title Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides
title_full Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides
title_fullStr Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides
title_full_unstemmed Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides
title_short Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides
title_sort inhibition of the rna-dependent rna-polymerase from sars-cov-2 by 6-chloropurine isoxazoline-carbocyclic monophosphate nucleotides
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552509/
https://www.ncbi.nlm.nih.gov/pubmed/37810686
http://dx.doi.org/10.1021/acsomega.3c04918
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