Aminopyridone-linked benzimidazoles: a fragment-based drug design for the development of CDK9 inhibitors.
Future Med Chem
; 15(14): 1213-1232, 2023 07.
Article
em En
| MEDLINE
| ID: mdl-37584185
ABSTRACT
Aim:
A fragment-based design and synthesis of three novel series of aminopyridone-linked benzimidazoles as potential anticancer candidates with significant CDK9 inhibition was implemented. Materials &methods:
All synthesized compounds were submitted to National Cancer Institute, 60 cell lines and seven-dose cytotoxicity toward three cancer cells.Results:
Compounds 2, 4a, 4c, 4d, 6a and 8a exhibited significant cytotoxicity and selectivity with IC50 range of 7.61-57.75 µM. Regarding the mechanism either in vitro or in silico, 4a, 6a and 8a displayed potent CDK9 inhibition with IC50 value of 0.424-8.461 µM. Compound 6a arrested the cell cycle at S phase and induced apoptosis in MCF-7 cells.Conclusion:
Compound 6a is a promising CDK9 inhibitor that warrants additional research for cancer treatment.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antineoplásicos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article