Discovery and pharmacophore studies of novel pyrazole-based anti-melanoma agents.
Chem Biodivers
; 12(1): 116-32, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25641840
ABSTRACT
Due to the rising incidence and lack of effective treatments, malignant melanoma is the most dangerous form of skin cancer, so that new treatment strategies are urgently needed. Several recent developments indicate that the V600E mutant BRAF (BRAF(V600E) ) is a validated target for antimelanoma-drug development. Based on in silico screening results, a series of novel pyrazole derivatives has been designed, synthesized, and evaluated in vitro for their inhibitory activities against BRAF(V600E) melanoma cells. Compound 3d exhibited the most potent inhibitory activity with an IC50 value of 0.63â
µM for BRAF(V600E) and a GI50 value of 0.61â
µM for mutant BRAF-dependent cells. Furthermore, the QSAR modeling and the docking simulation of inhibitor analogs provide important pharmacophore clues for further structural optimization.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Neoplasias Cutâneas
/
Descoberta de Drogas
/
Melanoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article