Dual-function antiandrogen/HDACi hybrids based on enzalutamide and entinostat.
Bioorg Med Chem Lett
; 55: 128441, 2022 01 01.
Article
en En
| MEDLINE
| ID: mdl-34767912
ABSTRACT
The combination of androgen receptor antagonists with histone deacetylase inhibitors (HDACi) has been shown to be more effective than antiandrogens alone in halting growth of prostate cancer cell lines. Here we have designed, synthesized and assessed a series of antiandrogen/HDACi hybrids by combining structural features of enzalutamide with either SAHA or entinostat. The hybrids are demonstrated to maintain bifunctionality using a fluorometric HDAC assay and a bioluminescence resonance energy transfer (BRET) antiandrogen assay. Antiproliferative assays showed that hybrids bearing o-aminoanilide-based HDACi motifs outperformed hydroxamic acid based HDACi's. The hybrids demonstrated selectivity for epithelial cell lines vs. stromal cell lines, suggesting a potentially useful therapeutic window.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Feniltiohidantoína
/
Piridinas
/
Benzamidas
/
Inhibidores de Histona Desacetilasas
/
Histona Desacetilasas
/
Antagonistas de Andrógenos
/
Antineoplásicos
/
Nitrilos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Canadá