Design, synthesis and biological characteristics of pyrazolo[3,4-d]pyrimidine derivatives as potential VEGFR-2 inhibitors.
Future Med Chem
; 14(22): 1649-1662, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-36317642
ABSTRACT
Aim:
Several VEGFR-2 inhibitors with the structure of [3,4-d]pyrimidine and based on sorafenib were designed and synthesized. Materials &methods:
Cytotoxic activity was evaluated by MTT, wound healing and clone formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Molecular simulation and western blot were also applied.Results:
Among them, II-1 significantly inhibited tumor cellular activity (IC50 = 5.90 ± 0.05 µM on HepG2 cells) compared with sorafenib (IC50 = 9.05 ± 0.54 µM on HepG2 cells). Molecular docking demonstrated that II-1 and sorafenib have the same hydrogen binding. Finally, the protein expression of phosphorylated VEGFR-2 was substantially reduced after II-1 treatment.Conclusion:
Compound II-1 can inhibit VEFGR-2 activation and is an effective antitumor agent in liver cancer cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article