Pharmacophore Modelling, Docking and Biological Evaluation of Vanillin Derivatives as Neuraminidase Inhibitors

A series of vanillin derivatives (1-3) were synthesized and their proposed structure was established by elemental analyses, FTIR and 1H-NMR spectral. In this paper we employed A 3D pharmacophore model based on selected ten established NA inhibitors as training set with diverse molecular structures and performed docking simulation using PDB-2HU0 to observe the ligand-protein complex interaction. The best hypothesis of the pharmacophore model consist one hydrogen bond acceptor (HBA), one hydrogen bond
donor (HBD) and one negative ionizable (NI) features used to predict the neuraminidase (NA) inhibition activities of the synthesized vanillin derivatives (1-3). All synthesized vanillin derivatives were tested against NA of clostridium perfringens on MUNANA assay for validation. The 4-[(4-Hydroxy-3- methoxybenzylidene)amino]-1,5-dimethyl-2-phenylpyrazolidin-3-one (1), 2-methoxyphenol-2,3,4-trimethyl-5- phenyl-1,3-oxazolidine (2) and 2-Methoxy-4-(phenylminomethyl)phenol (3) was found to inhibit the NA enzymes. These compounds exerted significant NA inhibition with IC50 0.73 mg/mL, 0.09 mg/mL and 0.26 mg/mL, respectively which is compared to the NA inhibitor, N-Acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) of IC50 0.2 mg/mL.