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

ID: ALA5252603

Journal: Bioorg Med Chem Lett

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

Authors: Shin YS, Lee JY, Jeon S, Myung S, Gong HJ, Kim S, Kim HR, Jeong LS, Park CM.

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.

CiteXplore: 36870624

DOI: 10.1016/j.bmcl.2023.129214

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