A Study of QSAR, Docking and Molecular Modeling of some Dihydropyrimidine Derivatives as Anticancer Agents

Abstract

Dihydropyrimidine derivatives are very important in synthetic medicinal chemistry because of their wide biological ranges in chemo therapy and drugs; this importance led to consider the activity of newly designed of dihydropyrimidine derivatives as macrophage migration (MIF) enzyme inhibitor. In this work the set of data was used to study quantitative structure activity relationship (QSAR) of dihydropyrimidine derivatives. The descriptors in two dimensional were removed because R2<0.7. The models obtained in three dimensional can be used to predict the activity of newly designed dihydropyrimidine derivatives against colon cancer as macrophage migration enzyme factor. A highly descriptive and predictive QSAR model was obtained through calculation of independent descriptors using MOE2009.10 software. A training set composed of 13compounds and obtained by partial least squares (PLS) analysis resulted in a model displaying a squared correlation coefficient (R2) of 0.889 (PIC50=5.213+ 0.373 npr2 -0.674MNDO-LUMO ). Validation of this model was performed using method leave-one-out (LOO) giving Q2 of 0.796 and R2pre of 0.979 for a test set of 3 compounds. This model was used to predict the biological activity of 94 new designed dihydropyrimidine derivatives and CHS828 was used as a reference compound. From these compounds 71 compounds which had a higher biological activity than a reference compound, were selected to study their affinity to colon cancer. Docking study for data set of 71 new designed compounds having high predicted activity to evaluate their interaction with protein of (MIF). In this study a number of compounds showed a goodness of interactions.