Molecular docking, pharmacophore modeling and 3D-QSAR approach on a series of piperidone derivatives as potential anticancer agents by targeting the enzyme VEGFR-2 tyrosine kinase

For a series of piperidone derivatives with anticancer activity against MCF7 cell lines pharmacophore modeling was performed by using PHASE, Partial least-squares (PLS) method was used to explore conformational space. All docking studies for the target compounds with VEGFR-2 tyrosine kinase were performed using GLIDE programme (Schrödinger Inc., USA). Statistically significant 3D-QSAR model was obtained through the pharmacophore hypothesis. A four-point pharmacophore with one hydrophobic (H), one hydrogen bond donor with positive ionic charge (P), and two aromatic rings (R) as pharmacophore features was developed with a correlation coefficient of r2 0.7586 and with a correlation coefficient of q² 0.532 for training set and test set of compounds, respectively with the excellent predictive power. The results provide insights that will facilitate the further structural modification of these anticancer agents for better activity, and may prove beneficial for lead optimization and in silico screening in future.