2-Pyridinyl-4(3H)-quinazolinone: a scaffold for anti-influenza A virus compounds.

A series of 2-pyridinyl-3-substituted-4(3H)-quinazolinones were synthesized, and their anti-influenza A virus activities were determined using the cytopathic effect inhibition assay. Most of the compounds were potent with IC50 values ranging from 51.6 to 93.0 μm, which are better than that of the currently marketed drug ribavirin. The molecular mechanisms of the new compounds were investigated using neuraminidase inhibition assay, cellular NF-κB signaling pathway inhibition assay, and computational docking. Compound 4e, which is a N3 imidazol-1-ylpropyl-substituted derivative of 2-pyridinyl-4(3H)-quinazolinone, had the most potent anti-influenza A virus activity in vitro, and inhibited both virus neuraminidase and cellular NF-κB signaling pathway. In conclusion, 2-pyridinyl-4(3H)-quinazolinone is a new scaffold for the design of potent anti-influenza A virus compounds, offering an alternative approach to tackle influenza drug resistance.