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

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 (ICs: 0.88-4.92 μM) were more active against IAV than Ribavirin. In particular, compound 9b exhibited broad-spectrum antiviral activity (IC: 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.