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Discovery of 2-Phenylquinolines with Broad-Spectrum Anti-coronavirus Activity
[Image: see text] A selection of compounds from a proprietary library, based on chemical diversity and various biological activities, was evaluated as potential inhibitors of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a phenotypic-based screening assay. A compound based on a...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088073/ https://www.ncbi.nlm.nih.gov/pubmed/35571875 http://dx.doi.org/10.1021/acsmedchemlett.2c00123 |
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author | Nizi, Maria Giulia Persoons, Leentje Corona, Angela Felicetti, Tommaso Cernicchi, Giada Massari, Serena Manfroni, Giuseppe Vangeel, Laura Barreca, Maria Letizia Esposito, Francesca Jochmans, Dirk Milia, Jessica Cecchetti, Violetta Schols, Dominique Neyts, Johan Tramontano, Enzo Sabatini, Stefano De Jonghe, Steven Tabarrini, Oriana |
author_facet | Nizi, Maria Giulia Persoons, Leentje Corona, Angela Felicetti, Tommaso Cernicchi, Giada Massari, Serena Manfroni, Giuseppe Vangeel, Laura Barreca, Maria Letizia Esposito, Francesca Jochmans, Dirk Milia, Jessica Cecchetti, Violetta Schols, Dominique Neyts, Johan Tramontano, Enzo Sabatini, Stefano De Jonghe, Steven Tabarrini, Oriana |
author_sort | Nizi, Maria Giulia |
collection | PubMed |
description | [Image: see text] A selection of compounds from a proprietary library, based on chemical diversity and various biological activities, was evaluated as potential inhibitors of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a phenotypic-based screening assay. A compound based on a 2-phenylquinoline scaffold emerged as the most promising hit, with EC(50) and CC(50) values of 6 and 18 μM, respectively. The subsequent selection of additional analogues, along with the synthesis of ad hoc derivatives, led to compounds that maintained low μM activity as inhibitors of SARS-CoV-2 replication and lacked cytotoxicity at 100 μM. In addition, the most promising congeners also show pronounced antiviral activity against the human coronaviruses HCoV-229E and HCoV-OC43, with EC(50) values ranging from 0.2 to 9.4 μM. The presence of a 6,7-dimethoxytetrahydroisoquinoline group at the C-4 position of the 2-phenylquinoline core gave compound 6g that showed potent activity against SARS-CoV-2 helicase (nsp13), a highly conserved enzyme, highlighting a potentiality against emerging HCoVs outbreaks. |
format | Online Article Text |
id | pubmed-9088073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-90880732022-05-11 Discovery of 2-Phenylquinolines with Broad-Spectrum Anti-coronavirus Activity Nizi, Maria Giulia Persoons, Leentje Corona, Angela Felicetti, Tommaso Cernicchi, Giada Massari, Serena Manfroni, Giuseppe Vangeel, Laura Barreca, Maria Letizia Esposito, Francesca Jochmans, Dirk Milia, Jessica Cecchetti, Violetta Schols, Dominique Neyts, Johan Tramontano, Enzo Sabatini, Stefano De Jonghe, Steven Tabarrini, Oriana ACS Med Chem Lett [Image: see text] A selection of compounds from a proprietary library, based on chemical diversity and various biological activities, was evaluated as potential inhibitors of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a phenotypic-based screening assay. A compound based on a 2-phenylquinoline scaffold emerged as the most promising hit, with EC(50) and CC(50) values of 6 and 18 μM, respectively. The subsequent selection of additional analogues, along with the synthesis of ad hoc derivatives, led to compounds that maintained low μM activity as inhibitors of SARS-CoV-2 replication and lacked cytotoxicity at 100 μM. In addition, the most promising congeners also show pronounced antiviral activity against the human coronaviruses HCoV-229E and HCoV-OC43, with EC(50) values ranging from 0.2 to 9.4 μM. The presence of a 6,7-dimethoxytetrahydroisoquinoline group at the C-4 position of the 2-phenylquinoline core gave compound 6g that showed potent activity against SARS-CoV-2 helicase (nsp13), a highly conserved enzyme, highlighting a potentiality against emerging HCoVs outbreaks. American Chemical Society 2022-05-03 /pmc/articles/PMC9088073/ /pubmed/35571875 http://dx.doi.org/10.1021/acsmedchemlett.2c00123 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Nizi, Maria Giulia Persoons, Leentje Corona, Angela Felicetti, Tommaso Cernicchi, Giada Massari, Serena Manfroni, Giuseppe Vangeel, Laura Barreca, Maria Letizia Esposito, Francesca Jochmans, Dirk Milia, Jessica Cecchetti, Violetta Schols, Dominique Neyts, Johan Tramontano, Enzo Sabatini, Stefano De Jonghe, Steven Tabarrini, Oriana Discovery of 2-Phenylquinolines with Broad-Spectrum Anti-coronavirus Activity |
title | Discovery of 2-Phenylquinolines with Broad-Spectrum
Anti-coronavirus Activity |
title_full | Discovery of 2-Phenylquinolines with Broad-Spectrum
Anti-coronavirus Activity |
title_fullStr | Discovery of 2-Phenylquinolines with Broad-Spectrum
Anti-coronavirus Activity |
title_full_unstemmed | Discovery of 2-Phenylquinolines with Broad-Spectrum
Anti-coronavirus Activity |
title_short | Discovery of 2-Phenylquinolines with Broad-Spectrum
Anti-coronavirus Activity |
title_sort | discovery of 2-phenylquinolines with broad-spectrum
anti-coronavirus activity |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088073/ https://www.ncbi.nlm.nih.gov/pubmed/35571875 http://dx.doi.org/10.1021/acsmedchemlett.2c00123 |
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