Construction of pharmacophore model of PARP-1 inhibitor.
- Author:
Wen-Ting ZHANG
1
;
Hao YAN
;
Feng-Chao JIANG
Author Information
1. School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
- Publication Type:Journal Article
- MeSH:
Computer-Aided Design;
Drug Design;
Enzyme Inhibitors;
chemistry;
pharmacology;
Models, Molecular;
Molecular Structure;
Poly (ADP-Ribose) Polymerase-1;
Poly(ADP-ribose) Polymerase Inhibitors;
Poly(ADP-ribose) Polymerases;
chemistry;
Protein Conformation
- From:
Acta Pharmaceutica Sinica
2007;42(3):279-285
- CountryChina
- Language:Chinese
-
Abstract:
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.
