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Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to threaten human health and create socioeconomic problems worldwide. A library of 200,000 small molecules from the Korea Chemical Bank (KCB) were evaluated for their inhibitory activities agai...

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Autores principales: Shin, Young Sup, Lee, Jun Young, Jeon, Sangeun, Myung, Subeen, Gong, Hyun June, Kim, Seungtaek, Kim, Hyoung Rae, Jeong, Lak Shin, Park, Chul Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier Ltd. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9979702/
https://www.ncbi.nlm.nih.gov/pubmed/36870624
http://dx.doi.org/10.1016/j.bmcl.2023.129214
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author Shin, Young Sup
Lee, Jun Young
Jeon, Sangeun
Myung, Subeen
Gong, Hyun June
Kim, Seungtaek
Kim, Hyoung Rae
Jeong, Lak Shin
Park, Chul Min
author_facet Shin, Young Sup
Lee, Jun Young
Jeon, Sangeun
Myung, Subeen
Gong, Hyun June
Kim, Seungtaek
Kim, Hyoung Rae
Jeong, Lak Shin
Park, Chul Min
author_sort Shin, Young Sup
collection PubMed
description The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to threaten human health and create socioeconomic problems worldwide. A library of 200,000 small molecules from the Korea Chemical Bank (KCB) were evaluated for their inhibitory activities against SARS-CoV-2 in a phenotypic-based screening assay to discover new therapeutics to combat COVID-19. A primary hit of this screen was the quinolone structure-containing compound 1. Based on the structure of compound 1 and enoxacin, which is a quinolone-based antibiotic previously reported to have weak activity against SARS-CoV-2, we designed and synthesized 2-aminoquinolone acid derivatives. Among them, compound 9b exhibited potent antiviral activity against SARS-CoV-2 (EC(50) = 1.5 µM) without causing toxicity, while having satisfactory in vitro PK profiles. This study shows that 2-aminoquinolone acid 9b provides a promising new template for developing anti-SARS-CoV-2 entry inhibitors.
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spelling pubmed-99797022023-03-03 Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2 Shin, Young Sup Lee, Jun Young Jeon, Sangeun Myung, Subeen Gong, Hyun June Kim, Seungtaek Kim, Hyoung Rae Jeong, Lak Shin Park, Chul Min Bioorg Med Chem Lett Article The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to threaten human health and create socioeconomic problems worldwide. A library of 200,000 small molecules from the Korea Chemical Bank (KCB) were evaluated for their inhibitory activities against SARS-CoV-2 in a phenotypic-based screening assay to discover new therapeutics to combat COVID-19. A primary hit of this screen was the quinolone structure-containing compound 1. Based on the structure of compound 1 and enoxacin, which is a quinolone-based antibiotic previously reported to have weak activity against SARS-CoV-2, we designed and synthesized 2-aminoquinolone acid derivatives. Among them, compound 9b exhibited potent antiviral activity against SARS-CoV-2 (EC(50) = 1.5 µM) without causing toxicity, while having satisfactory in vitro PK profiles. This study shows that 2-aminoquinolone acid 9b provides a promising new template for developing anti-SARS-CoV-2 entry inhibitors. The Author(s). Published by Elsevier Ltd. 2023-04-01 2023-03-02 /pmc/articles/PMC9979702/ /pubmed/36870624 http://dx.doi.org/10.1016/j.bmcl.2023.129214 Text en © 2023 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Shin, Young Sup
Lee, Jun Young
Jeon, Sangeun
Myung, Subeen
Gong, Hyun June
Kim, Seungtaek
Kim, Hyoung Rae
Jeong, Lak Shin
Park, Chul Min
Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2
title Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2
title_full Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2
title_fullStr Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2
title_full_unstemmed Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2
title_short Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2
title_sort discovery of 2-aminoquinolone acid derivatives as potent inhibitors of sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9979702/
https://www.ncbi.nlm.nih.gov/pubmed/36870624
http://dx.doi.org/10.1016/j.bmcl.2023.129214
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