Inhibition of the pore-forming protein perforin by a series of aryl-substituted isobenzofuran-1(3H)-ones.
Bioorg Med Chem
; 20(3): 1319-36, 2012 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-22244072
ABSTRACT
An aryl-substituted isobenzofuran-1(3H)-one lead compound was identified from a high throughput screen designed to find inhibitors of the lymphocyte pore-forming protein perforin. A series of analogs were then designed and prepared, exploring structure-activity relationships through variation of 2-thioxoimidazolidin-4-one and furan subunits on an isobenzofuranone core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 natural killer effector cells was determined. Several compounds showed excellent activity at concentrations that were non-toxic to the killer cells. This series represents a significant improvement on previous classes of compounds, being substantially more potent and largely retaining activity in the presence of serum.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Benzofuranos
/
Perforina
/
Inmunosupresores
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda