Pharmacoinformatics approach for mPGES-1 in anti-inflammation by 3D-QSAR pharmacophore mapping

Microsomal prostablandin E synthase-1 (mPGES-1) has been recently investigated to be a novel, hot, and promising target for inflammation-related diseases. The quantitative structure-activity relationship (QSAR) study was used to explore the critical pharmacophore features of mPGES-1 by using a set of 35 azaphenanthrenone derivatives. Twenty-four selected pharmacophore models derived from 240 hypotheses were employed to identify the critical features. The best two pharmacophore hypotheses, generated by HypoGen Technique, exhibited the residuals of approximately 150 and the high correlation coefficient of 0.92. The selected four hypotheses all showed a confidence level of 95% in the Fischer's randomization test. The final four pharmacophore model showed that the four dominant features (hydrogen bond donor and three hydrophobic features, occasionally replaced by ring aromatic feature) had significant impact on activity of mPGES-1 inhibitors. The database virtual screening and drug design can be further implement to searching the novel mPGES-1 inhibitors.