CoMFA/CoMSIA and Molecular Docking Studies of Novel Matrix Metalloproteinase- 2 Inhibitors Based on L-tyrosine Scaffold

Our previous studies showed that L-tyrosine derivatives possessed potential inhibitory activities against matrix metalloproteinase-2 (MMP-2), a target greatly embodied in tumor invasion and metastasis process. The CoMFA/CoMSIA and molecular docking analyses were performed to study the structure-activity relationships of these molecules. A data set of 21 L-tyrosine derivatives was used as the training set to derive the 3D-QSAR models, and 9 L-tyrosine derivatives was used as the test set to validate the models. Based on the molecular alignment, highly predictive CoMFA model was obtained with a crossvalidated q2 value of 0.542 and a conventional r2 of 0.998 in the non-cross-validated partial least-squares (PLS) analysis, while the CoMSIA model with a better predictive ability was shown with q2 and r2 values of 0.793 and 0.948, respectively. Contour maps derived from the 3D-QSAR models provided information on main factors towards the activity. In the docking studies, the docking scores and binding poses represented the detailed information about intermolecular interactions between the compound and the target protein. Therefore, combination of the CoMFA/CoMSIA and molecular docking results could be used in designing more potent MMP-2 inhibitors.