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.
- 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].
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.