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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s). Published by Elsevier Ltd.
2023
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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. |
format | Online Article Text |
id | pubmed-9979702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Author(s). Published by Elsevier Ltd. |
record_format | MEDLINE/PubMed |
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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