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

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=3.10-6.93μM) had good invitro activity against RSV, which were better than 1a and ribavirin. In addition, we found that compound 1g displayed the lower cytotoxicity (CC50: 2490.33μM) 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: 1.87-14.28μM) were more active against IAV than or comparable to ribavirin (IC50: 15.36±0.93μM). Particularly, the most active compound 1ae (IC50: 1.87±0.58μM) 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.