Discovery of novel human acrosin inhibitors by virtual screening.
J Comput Aided Mol Des
; 25(10): 977-85, 2011 Oct.
Article
en En
| MEDLINE
| ID: mdl-21984268
ABSTRACT
Human acrosin is an attractive target for the discovery of male contraceptive drugs. For the first time, structure-based drug design was applied to discover structurally diverse human acrosin inhibitors. A parallel virtual screening strategy in combination with pharmacophore-based and docking-based techniques was used to screen the SPECS database. From 16 compounds selected by virtual screening, a total of 10 compounds were found to be human acrosin inhibitors. Compound 2 was found to be the most potent hit (IC(50) = 14 µM) and its binding mode was investigated by molecular dynamics simulations. The hit interacted with human acrosin mainly through hydrophobic and hydrogen-bonding interactions, which provided a good starting structure for further optimization studies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Acrosina
/
Diseño de Fármacos
/
Inhibidores de Serina Proteinasa
/
Anticonceptivos Masculinos
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
J Comput Aided Mol Des
Asunto de la revista:
BIOLOGIA MOLECULAR
/
ENGENHARIA BIOMEDICA
Año:
2011
Tipo del documento:
Article