Discovery of novel VEGFR-2 inhibitors embedding 6,7-dimethoxyquinazoline and diarylamide fragments.
Bioorg Med Chem Lett
; 36: 127788, 2021 03 15.
Article
em En
| MEDLINE
| ID: mdl-33460739
ABSTRACT
VEGF/VEGFR-2 signaling plays a critical part in tumor angiogenesis. Inhibition of this pathway has been considered as a promising approach for cancer treatment. In this work, a series of 6,7-dimethoxy-4-anilinoquinazoline derivatives bearing diarylamide moiety were designed, synthesized and evaluated as potent inhibitors of VEGFR-2 kinase. Their in vitro antiproliferation activities against two human cancer cell lines Hep-G2 and MCF-7 have also been determined. Among them, compound 14b exhibited the most potent inhibitory activity against VEGFR-2 with IC50 value of 0.016 ± 0.002 µM and it showed the most potent antiproliferative effect against Hep-G2 and MCF-7 with IC50 values at low-micromolar range. Molecular docking studies revealed that these compounds represented by the most potent compound 14b could bind well to the ATP-binding site of VEGFR-2, which suggested that compound 14b could be a potential anticancer agent targeting VEGFR-2.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Receptor 2 de Fatores de Crescimento do Endotélio Vascular
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Inibidores de Proteínas Quinases
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Descoberta de Drogas
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Amidas
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Antineoplásicos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China