کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1359802 981415 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis, biological evaluation of novel 4,5-dihydro-2H-pyrazole 2-hydroxyphenyl derivatives as BRAF inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis, biological evaluation of novel 4,5-dihydro-2H-pyrazole 2-hydroxyphenyl derivatives as BRAF inhibitors
چکیده انگلیسی

A series of novel 4,5-dihydropyrazole derivatives (3a–3t) containing hydroxyphenyl moiety as potential V600E mutant BRAF kinase (BRAFV600E) inhibitors were designed and synthesized. Docking simulation was performed to insert compounds 3d (1-(5-(5-chloro-2-hydroxyphenyl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) and 3m (1-(3-(4-chlorophenyl)-5-(3,5-dibromo-2-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) into the crystal structure of BRAFV600E to determine the probable binding model, respectively. Based on the preliminary results, compound 3d and 3m with potent inhibitory activity in tumor growth may be a potential anticancer agent. Results of the bioassays against BRAFV600E, MCF-7 human breast cancer cell line and WM266.4 human melanoma cell line all showed several compounds had potent activities IC50 value in low micromolar range, among them, compound 3d and compound 3m showed strong potent anticancer activity, which were proved by that 3d: IC50 = 1.31 μM for MCF-7 and IC50 = 0.45 μM for WM266.5, IC50 = 0.22 μM for BRAFV600E, 3m: IC50 = 0.97 μM for MCF-7 and IC50 = 0.72 μM for WM266.5, IC50 = 0.46 μM for BRAFV600E, which were comparable with the positive control Erlotinib.

A series of novel 4,5-dihydropyrazole derivatives (3a–3t) containing hydroxyphenyl moiety as potential V600E mutant BRAF kinase (BRAFV600E) inhibitors were designed and synthesized. Docking simulation was performed to insert compounds 3d and 3m into the crystal structure of BRAFV600E to determine the probable binding model, respectively. Based on the preliminary results, compound 3d and 3m with potent inhibitory activity in tumor growth may be a potential anticancer agent. Results of the bioassays against BRAFV600E, MCF-7 human breast cancer cell line and WM266.4 human melanoma cell line all showed several compounds had potent activities IC50 value in low micromolar range, among them, compound 3d and compound 3m showed strong potent anticancer activity, which were proved by that 3d: IC50 = 1.31 μM for MCF-7 and IC50 = 0.45 μM for WM266.5, IC50 = 0.22 μM for BRAFV600E, 3m: IC50 = 0.97 μM for MCF-7 and IC50 = 0.72 μM for WM266.5, IC50 = 0.46 μM for BRAFV600E, which were comparable with the positive control Erlotinib.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 20, 15 October 2012, Pages 6089–6096
نویسندگان
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