Simplified molecular input line entry system-based: QSAR modelling for MAP kinase-interacting protein kinase (MNK1)

Abstract

Quantitative structure–activity relationship (QSAR) models were built for the prediction of inhibition (pIC50, i.e. negative logarithm of the 50% effective concentration) of MAP kinase-interacting protein kinase (MNK1) by 43 potent inhibitors. The pIC50 values were modelled with five random splits, with the representations of the molecular structures by simplified molecular input line entry system (SMILES). QSAR model building was performed by the Monte Carlo optimisation using three methods: classic scheme; balance of correlations; and balance correlation with ideal slopes. The robustness of these models were checked by parameters as rm2, r*m2, and randomisation technique. The best QSAR model based on single optimal descriptors was applied to study in vitro structure–activity relationships of 6-(4-(2-(piperidin-1-yl) ethoxy) phenyl)-3-(pyridin-4-yl) pyrazolo [1,5-a] pyrimidine derivatives as a screening tool for the development of novel potent MNK1 inhibitors. The effects of alkyl group, –OH, –NO2, F, Cl, Br, I, etc. on the IC50 values towards the inhibition of MNK1 were also reported.