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

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

  • Bioorg Med Chem Lett. 2023 Apr 1:85:129214. doi: 10.1016/j.bmcl.2023.129214.
Young Sup Shin 1,  Jun Young Lee 1,  Sangeun Jeon 2,  Subeen Myung 3,  Hyun June Gong 4,  Seungtaek Kim 2,  Hyoung Rae Kim 5,  Lak Shin Jeong 6,  Chul Min Park 7
Affiliations

Affiliations

  • 1 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Republic of Korea.
  • 2 Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, Republic of Korea.
  • 3 Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology, Daejeon 34114, Republic of Korea.
  • 4 Department of Chemistry, Chungnam National University, Daejeon 34134, Republic of Korea.
  • 5 Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Republic of Korea.
  • 6 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: [email protected].
  • 7 Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology, Daejeon 34114, Republic of Korea. Electronic address: [email protected].
PMID: 36870624 DOI: 10.1016/j.bmcl.2023.129214
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.

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