Inhibition of microsomal prostaglandin E synthase-1 by phenanthrene imidazoles: a QSAR study

Quantitative structure-activity relationships have been developed to predict the inhibitory activity of phenanthrene imidazoles toward mPGES-1. The dataset was divided into training and test set by random selection. Models were developed with partial least squares regression method. All the models have been validated internally, externally, and by randomization technique. 2DQSAR revealed that the polarization of the molecule in the Y plane is a critical factor for binding to mPGES-1. 3DQSAR suggests that the shape of the active site is V-Shaped, and hence, the triangular phenanthrene imidazole molecules fit well utilizing van der Waals interactions as a major force for binding. Group-QSAR suggests that substitutions at R3, R5, and R8 positions are crucial for mPGES-1 inhibitory activity.