Jump to main content
Jump to site search

Issue 37, 2013
Previous Article Next Article

Synthesis, biological evaluation and molecular docking of novel 5-phenyl-1H-pyrazol derivatives as potential BRAFV600E inhibitors

Author affiliations

Abstract

The RAF–MEK–ERK cascade appears to be intimately involved in the regulation of cell cycle progression and apoptosis. The BRAFV600E mutant results in constitutive activation of the ERK pathway, which can lead to cellular growth dysregulation. A series of 5-phenyl-1H-pyrazol derivatives (3a–5e) have been designed and synthesized, and their biological activities were evaluated as potential BRAFV600E inhibitors. All the compounds were reported for the first time except 3e, and compound 1-(4-bromo-2-hydroxybenzyl)-3-phenyl-1-(5-phenyl-1H-pyrazol-3-yl)urea (5c) displayed the most potent inhibitory activity (BRAFV600E IC50 = 0.19 μM). Antiproliferative assay results indicated that compound 5c possessed high antiproliferative activity against cell lines WM266.4 and A375 in vitro, with IC50 values of 1.50 and 1.32 μM, respectively, which were comparable with the positive control vemurafenib. Docking simulations showed that compound 5c binds tightly to the BRAFV600E active site and acts as BRAFV600E inhibitor. A 3D-QSAR model was also built to provide more pharmacophore understanding towards designing new agents with more potent BRAFV600E inhibitory activity.

Graphical abstract: Synthesis, biological evaluation and molecular docking of novel 5-phenyl-1H-pyrazol derivatives as potential BRAFV600E inhibitors

Back to tab navigation

Supplementary files

Publication details

The article was received on 17 Apr 2013, accepted on 05 Jun 2013 and first published on 05 Jul 2013


Article type: Paper
DOI: 10.1039/C3OB40776D
Citation: Org. Biomol. Chem., 2013,11, 6328-6337
  •   Request permissions

    Synthesis, biological evaluation and molecular docking of novel 5-phenyl-1H-pyrazol derivatives as potential BRAFV600E inhibitors

    J. Dong, Q. Li, S. Wang, C. Li, X. Zhao, H. Qiu, M. Zhao and H. Zhu, Org. Biomol. Chem., 2013, 11, 6328
    DOI: 10.1039/C3OB40776D

Search articles by author

Spotlight

Advertisements