Construction of pharmacophore model of PARP-1 inhibitor

To construct the pharmacophore model of the poly(ADP-ribose) polymerase-1 inhibitor and to investigate the possible inhibitory mechanisms, ten pharmacophore models of PARP-1 inhibitor were established from the training set of thirty-eight PARP-1 inhibitors with conformer analysis and pharmacophore mapping by using the Catalyst software. Based on the mechanism of action and the known structure-activity relationship of PARP-1 inhibitor, an optimal pharmacophore model including two hydrogen-bonding acceptors and two aromatic hydrophobic core was confirmed. The reliability of the optimal pharmacophore model is preferably with RMS=0.46, Correl=0.91, Weight=2.06, and Config=15.97. This pharmacophore model not only provided some information about the interaction between enzyme and compound, but also showed excellent forecast ability and contributes to design the PARP-1 inhibitors with undiscovered structure.