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

Abstract

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 (EC50 = 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.

• Authors: Young Sup Shin, Jun Young Lee, Sangeun Jeon, Subeen Myung, Hyun June Gong, Seungtaek Kim, Hyoung Rae Kim, Lak Shin Jeong, Chul Min Park
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 85 Pg. 129214 (04 01 2023) ISSN: 1464-3405 [Electronic] England
• PMID: 36870624 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• aminoquinolone
• Antiviral Agents
• Protease Inhibitors

Topics

• Humans
• SARS-CoV-2
• COVID-19
• Pandemics
• Antiviral Agents (pharmacology, chemistry)
• Molecular Docking Simulation
• Protease Inhibitors