Design, synthesis and biological evaluation of dual Bcl-2/Mcl-1 inhibitors bearing 2-(1H-indol-4-yl)benzoic acid scaffold.
Bioorg Med Chem Lett
; 47: 128215, 2021 09 01.
Article
em En
| MEDLINE
| ID: mdl-34153472
ABSTRACT
The anti-apoptotic protein inhibitors of the B cell lymphoma 2 (Bcl-2) family have been developed as new anticancer therapies. Numerous studies illustrated the great potential in the development of dual Bcl-2/myeloid cell leukemia 1 (Mcl-1) inhibitors. Herein, we reported a series of Bcl-2/Mcl-1 inhibitors that optimized from a hit compound 1 via structure-based rational design. The biological evaluation suggested that most compounds exhibited potent binding affinities at submicromolar to both Bcl-2 and Mcl-1 without any Bcl-xL binding affinities, especially compound 9o, with a Ki value of 0.07 µM to Mcl-1 and 0.66 µM to Bcl-2, that has great potential for developing dual inhibitors targeting Bcl-2 and Mcl-1.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Proteína de Sequência 1 de Leucemia de Células Mieloides
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China