Abstract
Influenza A viruses have caused worldwide epidemics and pandemics by reassortment and generation of drug-resistant mutants, which leads to an urgent need to develop novel antivirals. In this study, a series of sulfonyl piperazine nucleozin derivatives were designed and synthesized, and their in vitro anti-influenza activity was evaluated. Many of these compounds exhibited moderate to good anti-influenza activity against influenza A. Among these, 6d, 6g, 6h, 6i, and 6j exhibited better activity than ribavirin. 2,3-dichlorobenzene substituted analogue 6i displayed the most remarkable in vitro activity against Influenza A. All the derivatives show no obvious cellular growth inhibition against MDCK cells. This study reported a new series of nucleoprotein inhibitors with a good selectivity window and potential for further development as novel anti-influenza agents.
Keywords: Anti-influenza A, Nucleoprotein, Sulfonyl Piperazine derivatives, Drug design, Synthesis, biological evaluation
Graphical Abstract
[http://dx.doi.org/10.1021/acs.jmedchem.5b01933] [PMID: 27120583]
[http://dx.doi.org/10.1016/j.vaccine.2021.08.010] [PMID: 34602302]
[http://dx.doi.org/10.1016/j.vaccine.2021.07.057] [PMID: 34376307]
[http://dx.doi.org/10.1016/j.antiviral.2020.104828] [PMID: 32574689]
[http://dx.doi.org/10.4103/0974-777X.100581] [PMID: 23055650]
[http://dx.doi.org/10.1016/j.ijid.2022.04.045] [PMID: 35477049]
[http://dx.doi.org/10.1016/j.vetmic.2021.109303] [PMID: 34923246]
[http://dx.doi.org/10.1016/j.heliyon.2021.e08384] [PMID: 34825090]
[http://dx.doi.org/10.1021/jm300455c] [PMID: 22612288]
[http://dx.doi.org/10.1016/j.antiviral.2020.104780] [PMID: 32229237]
[http://dx.doi.org/10.1016/j.virol.2017.06.011] [PMID: 28644977]
[http://dx.doi.org/10.1016/j.ejmech.2021.113762] [PMID: 34411893]
[http://dx.doi.org/10.1016/j.jiac.2021.11.014] [PMID: 34840038]
[http://dx.doi.org/10.1016/j.antiviral.2013.03.014] [PMID: 23523943]
[http://dx.doi.org/10.1016/j.bbrc.2019.08.126] [PMID: 31474336]
[http://dx.doi.org/10.1016/j.ijbiomac.2021.01.076] [PMID: 33454328]
[http://dx.doi.org/10.1016/0092-8674(81)90208-7] [PMID: 7326745]
[http://dx.doi.org/10.1128/jvi.64.4.1487-1497.1990] [PMID: 2319644]
[http://dx.doi.org/10.1155/2011/939860] [PMID: 22007149]
[http://dx.doi.org/10.1016/j.antiviral.2019.01.002] [PMID: 30639307]
[http://dx.doi.org/10.1038/nbt.1638] [PMID: 20512121]
[http://dx.doi.org/10.1073/pnas.1013592107] [PMID: 20974907]
[http://dx.doi.org/10.1073/pnas.1107906108] [PMID: 21896751]
[http://dx.doi.org/10.1021/jm2013503] [PMID: 22332894]
[http://dx.doi.org/10.1039/C9RA10828A] [PMID: 35495231]
[http://dx.doi.org/10.1016/j.tetlet.2012.12.106]