Design, synthesis and CoMFA studies of N1-amino acid substituted 2,4,5-triphenyl imidazoline derivatives as p53-MDM2 binding inhibitors.
Bioorg Med Chem
; 20(4): 1417-24, 2012 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-22273545
ABSTRACT
A series of novel N1-amino-acid substituted 2,4,5-triphenyl imidazoline derivatives was designed and synthesized based on our previous studies. All synthesized target compounds were screened for their p53-MDM2 binding inhibitory activities and anti-proliferative activities against five cancer cell lines. Among them, twelve compounds displayed improved binding inhibitory activities and most compounds showed higher cell growth inhibition activities with IC(50) values in the low micromolar range. Compound 6c exhibited marked p53-MDM2 binding inhibitory activity (IC(50)=0.59 µM) which was eightfold more potent than that of Nutlin-1 (IC(50)=4.78 µM). CoMFA analysis was performed based on obtained biological data and resulted in a statistically significant CoMFA model with high predict abilities (q(2)=0.645, r(2)=0.979).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
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Imidazolinas
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Proteínas Proto-Oncogênicas c-mdm2
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Modelos Biológicos
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
China