Construction of pharmacophore model of PARP-1 inhibitor / 药学学报
Acta Pharmaceutica Sinica
; (12): 279-285, 2007.
Article
em Zh
| WPRIM
| ID: wpr-281907
Biblioteca responsável:
WPRO
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.
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Farmacologia
/
Conformação Proteica
/
Desenho de Fármacos
/
Estrutura Molecular
/
Modelos Moleculares
/
Química
/
Poli(ADP-Ribose) Polimerases
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Desenho Assistido por Computador
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Inibidores Enzimáticos
/
Inibidores de Poli(ADP-Ribose) Polimerases
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Ano de publicação:
2007
Tipo de documento:
Article