Modelling of Schiff Base Vanillin Derivatives Targeting Streptococcus Pneumoniae Bacterial Neuraminidase
Keywords:
Molecular docking, neuraminidase, pharmacophore modelling, Schiff base vanillin derivatives, Streptococcus pneumoniaeAbstract
Streptococcus pneumoniae is a pathogenic bacterium which has led to serious pneumococcal infections. Despite the fact that efficient therapeutic agents and vaccinations are available for the treatment of Streptococcus pneumoniae infections, more strains of Streptococcus pneumoniae have acquired significant resistance towards the available antibiotics. The neuraminidase of Streptococcus pneumoniae possess significant contribution in pathogenesis, aiding the release and spread of virus. Simultaneously, Schiff base vanillin derivatives were reported in past literature for their great deal of potential as inhibitors of influenza virus neuraminidase. Hence, the research aims to evaluate the inhibitory activity of Schiff base vanillin derivatives against Streptococcus pneumoniae neuraminidase via ligand-based pharmacophore modelling and structure-based molecular docking using LigandScout 4.4.9 and AutoDock 4.2. Ligand-based pharmacophore modelling was performed to analyse the anti-neuraminidase activity of Schiff base vanillin derivatives based on their pharmacophore fit values and matching pharmacophore features with a pharmacophore model, generated from a list of training sets, which are reported drugs against Streptococcus pneumoniae neuraminidase. In structure-based molecular docking, the Schiff base vanillin derivatives were evaluated based on their docking performances with the active sites of the crystal structure of PDB:2YA8. Evaluations were based on their pharmacophore scores, binding affinity and matching interactions with the inhibitory ligand of 2YA8. 20 out of 21 Schiff base vanillin derivatives successfully show good results in ligand-based pharmacophore modelling, as well as satisfying docking performances in structure-based molecular docking. Furthermore, they also fulfill the Lipinski’s Rule of 5, thus displaying appreciable potential as inhibitors of Streptococcus pneumoniae neuraminidase.
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