2. Academic Validation
  3. Synthesis and antiviral activity of a series of novel quinoline derivatives as anti-RSV or anti-IAV agents

Synthesis and antiviral activity of a series of novel quinoline derivatives as anti-RSV or anti-IAV agents

  • Eur J Med Chem. 2021 Mar 15:214:113208. doi: 10.1016/j.ejmech.2021.113208.
Minghua Wang 1,  Guoning Zhang 1,  Jianyuan Zhao 1,  Ningning Cheng 2,  Yujia Wang 1,  Yuanhui Fu 2,  Yanpeng Zheng 2,  Juxian Wang 1,  Mei Zhu 1,  Shan Cen 3,  Jinsheng He 4,  Yucheng Wang 5
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
  • 2 College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China.
  • 3 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: [email protected].
  • 4 College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. Electronic address: [email protected].
  • 5 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: [email protected].
PMID: 33571829 DOI: 10.1016/j.ejmech.2021.113208
Abstract

We report herein the synthesis of a series of novel quinoline derivatives, based on the lead compound 1a, identified from a rRSV-mGFP high-throughput screening assay. Our results revealed that target compounds 1b, 1g-h, 1af and 1ah (IC50 = 3.10-6.93 μM) had good in vitro activity against RSV, which were better than 1a and ribavirin. In addition, we found that compound 1g displayed the lower cytotoxicity (CC50: 2490.33 μM) and the highest selective index (SI = 673.06), suggesting its promising potential as a candidate for further development. On the Other hand, compounds 1a, 1m, 1v, 1ad-1af and 1ah-1ai (IC50s: 1.87-14.28 μM) were more active against IAV than or comparable to ribavirin (IC50: 15.36 ± 0.93 μM). Particularly, the most active compound 1ae (IC50: 1.87 ± 0.58 μM) was found to be 8.2-fold more potent than the reference drug, which could inhibit the virus transcription and replication cycle at an early stage.

Keywords

Anti-IAV; Anti-RSV; Quinoline derivatives; Structure-activity relationships; Synthesis.

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