Synthesis and biological evaluation of 1H-pyrrolo[3,2-g]isoquinolines.
Bioorg Med Chem
; 100: 117619, 2024 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-38320389
ABSTRACT
A structure-activity relationship study performed on 1H-pyrrolo[3,2-g]isoquinoline scaffold identified new haspin inhibitors with nanomolar potencies and selectivity indices (SI) over 6 (inhibitory potency evaluated against 8 protein kinases). Compound 22 was the most active of the series (haspin IC50 = 76 nM). Cellular evaluation of 22 confirmed its activity for endogenous haspin in U-2 OS cells and its anti-proliferative activity against various cell lines. In addition, the binding mode of analog 22 in complex with haspin was determined by X-ray crystallography.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Proteínas Serina-Treonina Quinases
/
Inibidores de Proteínas Quinases
Idioma:
En
Revista:
Bioorg Med Chem
/
Bioorg. med. chem
/
Bioorganic & medicinal chemistry
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França