3D-QSAR and Docking Studies on Pyrimidine Derivatives as CSF-1R Inhibitors

Abstract

Background: Colony Stimulating Factor-1 Receptor (CSF-1R) is associated with malignancy, invasiveness and poor prognosis of tumors, and pyrimidine derivatives are considered as a novel class of CSF-1R inhibitor. Methods: To explore the relationship between the structures of substituted pyrimidine derivatives and their inhibitory activities against CSF-1R, CoMFA and CoMSIA analyses, and molecular docking studies were performed on a dataset of forty-four compounds. Results: We found in CoMFA model including steric and electrostatic fields for the training set, the cross-validated q2 value was 0.617 and the non-cross-validated r2 value was 0.983. While, the crossvalidated q2 value was 0.637 and the non-cross-validated r2 value was 0.984 in CoMSIA Model which include steric, electrostatic and hydrophobic fields. 3D equipotential maps generated from CoMFA and CoMSIA along with the docking binding structures provided enough information about the structural requirements for better activity. Conclusion: The data generated from the present study helped us to predict the activity of new inhibitors and further design some novel and potent CSF-1R inhibitors.