Figure 1.
Step-wise description ofmethodology used for 3D-QSAR analysis, molecular docking and designing of new inhibitors for CDK4.
Figure 2.
Chemical structures and IC50 values of the training and test set molecules.
Figure 3.
Alignment of the compounds used in the training set.
Figure 4.
Graph of actual versus predicted pIC50 of the training set and the test set using CoMFA (Left) and CoMSIA (Right).
Table 1.
PLS results of CoMFA and CoMSIA models.
Table 2.
The actual pIC50, predicted pIC50 (Pred.) and their residuals (Res.) of the training and test set molecules.
Table 3.
Results of the external validation for CoMFA and CoMSIA models.
Figure 5.
Std* coeff contour maps of CoMFA analysis in combination with compound 12.
(a) Steric fields: green contours suggest regions where bulky groups increase activity, while yellow contours indicate regions where bulky groups decrease activity, and (b) Electrostatic fields: blue contours represent regions where electron-donating groups increase activity, while red contours highlight regions where electron-withdrawing groups increase activity.
Figure 6.
Std* coeff contour maps of CoMSIA in combination with compound 12.
(a) Steric contour map. Green and yellow contours refer to sterically favored and unfavored regions. (b) Electrostatic contour map. Blue and red contours refer to regions where electron-donating and electron withdrawing groups are favored. (c) Hydrophobic contour map. White and yellow contours represent regions where hydrophilic and hydrophobic substituent are favored. (d) Hydrogen bond donor contour map. The cyan and purple contours indicate favorable and unfavorable hydrogen bond donor groups. (e) Hydrogen bond acceptor contour map. The magenta and red contours demonstrated favorable and unfavorable hydrogen bond acceptor groups.
Figure 7.
The binding mode between selected compound 12 and the ATP pocket of CDK4 (PDB code: 1GIH).
Figure 8.
Structure-activity relationship revealed by 3D-QSAR and docking studies.
Figure 9.
Structures and predicted pIC50 values of newly designed molecules.