The threat of influenza pandemic and the emergence of viral resistance towards the existing NA inhibitors have prompted the needs for the discovery of new NA inhibitors. Here, we report the computational and experimental efforts in the synthesis of potential NA inhibitors from ferulic acid and vanillin. Two targeted ferulic acid analogues, MY7 and MY8 were predicted their mechanism to inhibit NA using molecular docking and pharmacophore mapping. From these two analogues, we modeled, synthesized and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. From the enzymatic H1N1 NA inhibition assay, MY23, a vanillin derivative showed the lowest IC50 of 50 mM but the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the IC50 ~0.95 mM. Based on the constructed QSAR model, MY7 and MY8, the targeted compounds, were predicted to have good NA inhibitory activities with IC50 2.0 and 3.0 mM, respectively thus strengthening our earlier prediction that these two compounds might be good starting structures for further optimization of ferulic acid and vanillin derivatives. These predicted activities might be due to their interactions with conserved and essential residues of NA such as Arg118, Asp151, Arg152, Glu227, Glu277, Arg371 and Tyr406 with a comparable DGbind to oseltamivir and zanamivir, commercial NA inhibitors. It is hoped that the results from this study could provide an insight into the design of novel and potent inhibitors based on a cheap chemical scaffold such as that of ferulic acid or vanillin.

Ferulic acid and vanillin analogues as potential influenza neuraminidase inhibitors: Modelling, synthesis and biological activities

251st National Meeting (2016)

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