Design, synthesis and in vitro biological evaluation of isoxazol-4-carboxa piperidyl derivatives as new anti-influenza A agents targeting virus nucleoprotein

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Abstract

Influenza infection is a major cause of morbidity and mortality during seasonal epidemics and sporadic pandemics. It is important and urgent to develop new anti-influenza agents with a new mechanism of action. Nucleozin has been reported as a potent antagonist of nucleoprotein accumulation in the nucleus. In this study, a new series of isoxazol-4-carboxa piperidyl derivatives 1a-j were synthesized and their chemical structures were confirmed by 1H, 13C NMR and mass spectral data. Furthermore, all the synthesized compounds were evaluated for in vitro anti-influenza virus activity against influenza virus (A/PR/8/34 H1N1). Among all the compounds, 1a, 1b, 1c, 1f and 1g exhibited more potent activity than the standard drug, and compound 1b has showed most promising anti-influenza virus activity. These results are also consistent with the docking study results in terms of the design of compounds targeting influenza A via viral nucleoprotein.

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Pei, S., Xia, S., Yang, F., Chen, J., Wang, M., Sun, W., … Chen, J. (2020). Design, synthesis and in vitro biological evaluation of isoxazol-4-carboxa piperidyl derivatives as new anti-influenza A agents targeting virus nucleoprotein. RSC Advances, 10(8), 4446–4454. https://doi.org/10.1039/c9ra10828a

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