Design,synthesis and anti-influenza activity of 2-[(quinoline-4-yl)amino]benzoic acid and 2-[(quinoline-4-yl)amino]benzamide derivatives
Influenza can cause severe respiratory diseases and seriously endanger human health.Nucleoprotein plays an important role in the replication,transcription and translation of influenza viruses and has been reported as a new drug target for anti-influenza drug design.Arg416 in the nucleoprotein tail loop can form a salt bridge interaction with Glu339 in another nucleoprotein monomer to ensure the normal generation of nucleoprotein oligomers as reported.Thus,we could design and synthesize compounds formed interaction with Glu339 to inhibit the interaction between Glu339 and Arg416.Then,the reproduction of influenza virus could not proceed normally.2-[(Quinoline-4-yl)amino]benzoic acid/2-[(quinoline-4-yl)amino]benzamide derivatives were designed according to the reported compounds.The results of molecular docking show that the target compounds after structural modification can interact well with Glu339 of nucleoprotein(PDB ID:2IQH).The cytotoxicity and anti-influenza virus activity of 15 target compounds were tested.The results of cytotoxicity assay,cytopathic effect assay and plaque inhibition assay show that most of the target compounds have low cytotoxicity and improve the viability of MDCK cells infected by influenza virus in varying degrees.Furthermore,compound 6a exhibits potent anti-influenza virus activity and is valuable for further research.
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