Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry.
Bioorg Med Chem
; 26(12): 3145-3157, 2018 07 23.
Article
em En
| MEDLINE
| ID: mdl-29859750
ABSTRACT
The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089⯱â¯0.007⯵M, which was two orders of magnitude lower than that of bestatin (IC50â¯=â¯9.4⯱â¯0.5⯵M). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10⯵M), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100⯵M in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Antígenos CD13
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Leucina
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Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article