Discovery of Dioxino[2,3-f]quinazoline derivative VEGFR-2 inhibitors exerting significant antipro-liferative activity in HUVECs and mice.
Eur J Med Chem
; 175: 349-356, 2019 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-31096155
ABSTRACT
Twelve 2,3-dihydro-[1,4]-dioxino[2,3-f]quinazoline derivatives were designed and evaluated as vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors. The most half-maximal inhibitory concentration (IC50) values of them were less than 10â¯nM. Among these compounds, 13d displayed highly effective inhibitory activity against VEGFR-2 (IC50â¯=â¯2.4â¯nM) and excellent antiproliferative activities against human umbilical vein endothelial cells (HUVECs) (IC50â¯=â¯1.2â¯nM). When anti-tumor animal experiments were carried out in mice, the tumor almost disappeared (TGIâ¯=â¯133.0%) after six days of administration of 13d. Therefore, 13d was a potential and effective anticancer agent. The binding conformations were respectively compared between VEGFR-2 with 13d and leading compound lenvatinib, and shows that they have similar binding modes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Inibidores da Angiogênese
/
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
/
Proliferação de Células
/
Descoberta de Drogas
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
FR
/
FRANCE
/
FRANCIA
/
FRANÇA