Synthesis and biological evaluation of substituted quinolines containing piperazine moieties against Influenza A virus

  • Bioorg Med Chem Lett. 2024 Dec 24:118:130081. doi: 10.1016/j.bmcl.2024.130081.
Hongxuan Li  1 ,  Jianyuan Zhao  1 ,  Fangyi Jiang  1 ,  Chenghong Zheng  1 ,  Guoning Zhang  1 ,  Mei Zhu  1 ,  Shan Cen  1 ,  Minghua Wang  2 ,  Yucheng Wang  3 ,  Juxian Wang  4
Affiliations
  • 1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
  • 3. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
  • 4. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
PMID: 39724985 DOI: 10.1016/j.bmcl.2024.130081
Abstract

Influenza A virus (IAV) poses a serious global threat to public health. There is an urgent need to develop new anti-IAV agents due to the limitations of the current Antiviral drugs in clinical practice. Herein, based on compound I-13e, we designed and synthesized 23 substituted quinoline derivatives containing piperazine moieties and evaluated their in vitro anti-IAV activity. The results showed that compounds 4a, 4c, 6c, 6f, 6g, 6i and 9a-9d (IC50s: 0.88-4.92 μM) were more active against IAV than Ribavirin. In particular, compound 9b exhibited broad-spectrum Antiviral activity (IC50: 0.88-6.33 μM) and acceptable cytotoxicity. The preliminary studies on its mechanism of action indicated an inhibition of viral RNA transcription and replication. These results suggested its potential as a promising anti-IAV candidate for further investigation.

Keywords
Anti-IAV; Structure-activity relationships; Substituted quinolines; Synthesis.
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