AI Article Synopsis
- A series of 5-phenyl-1H-pyrazole derivatives, containing a niacinamide group, were synthesized and tested for their ability to inhibit the BRAF(V600E) enzyme.
- Compound 5h stood out as the most effective inhibitor, demonstrating a potent IC50 value of 0.33 μM, and showed good antiproliferative activity against melanoma cell lines WM266.4 and A375, closely matching the performance of the positive control vemurafenib.
- Molecular docking studies were conducted on compound 5h to analyze its binding interactions with BRAF(V600E), alongside 3D quantitative structure-activity relationship (QSAR) assessments to further
Article Abstract
A series of novel 5-phenyl-1H-pyrazole derivatives (5 a-5 u) containing niacinamide moiety were synthesized and evaluated for biological activity as potential BRAF(V600E) inhibitors. Among them, compound 5h exhibited the most potent inhibitory activity with an IC50 value of 0.33 μM for BRAF(V600E). Antiproliferative assay results indicated that compound 5h has better antiproliferative activity against WM266.4 and A375 in vitro with IC50 value of 2.63 and 3.16 μM, respectively, being comparable with the positive control vemurafenib. Molecular docking of 5h into the BRAF(V600E) active site was performed to determine the probable binding mode. Furthermore, molecular docking and 3D QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives.
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| http://dx.doi.org/10.1016/j.bmc.2014.08.029 | DOI Listing |
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Article Synopsis
- A series of 5-phenyl-1H-pyrazole derivatives, containing a niacinamide group, were synthesized and tested for their ability to inhibit the BRAF(V600E) enzyme.
- Compound 5h stood out as the most effective inhibitor, demonstrating a potent IC50 value of 0.33 μM, and showed good antiproliferative activity against melanoma cell lines WM266.4 and A375, closely matching the performance of the positive control vemurafenib.
- Molecular docking studies were conducted on compound 5h to analyze its binding interactions with BRAF(V600E), alongside 3D quantitative structure-activity relationship (QSAR) assessments to further
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