QSAR study of tetrahydropteridin derivatives as polo-like kinase 1(PLK1) Inhibitors with molecular docking and dynamics study

PLK1 is the key target for dealing with different cancer because it plays an important role in cell proliferation. According to the regulation of OECD, a QSAR model was developed from a dataset of 68 tetrahydropteridin derivatives. Three descriptors (maxHaaCH, ATSC7i, AATS7m) were considered for the development of the QSAR model. The reliability and predictability of the developed QSAR model were evaluated by various statistical parameters (<i>r</i>² = 0.8213, <i>r</i>²_ext = 0.8771 and CCC_ext = 0.9364). The maxHaaCH descriptor is positively correlated to pIC₅₀ whereas, the ATSC7i and AATS7m are negatively correlated with pIC₅₀. The QSAR model explains all the structural features and shows a good correlation with the activity. Based on molecular modelling techniques, five compounds (D1-D5) were designed. Molecular docking and dynamics studies of the most active compound were performed with PDB ID: 2RKU. The results of the present investigation may be employed to identify and develop effective inhibitors for the treatment of PLK1-related pathophysiological disorders.