Discovery and Pharmacophore Studies of Novel Pyrazole‐Based Anti‐Melanoma Agents |
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| Authors: | Qing‐Shan Li Xian‐Hai Lü Yang Yang Ban‐Feng Ruan Ri‐Sheng Yao Chen‐Zhong Liao |
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| Institution: | 1. School of Medical Engineering, Hefei University of Technology, Hefei 230009, P.?R. China, (phone/fax: +86‐551‐62904675);2. Key Laboratory of Green Pesticide and Agriculture Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, P.?R. China;3. College of Science, Anhui Agricultural University, Hefei 230036, P.?R. China;4. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, P.?R. China |
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| 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 (BRAFV600E) 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 BRAFV600E melanoma cells. Compound 3d exhibited the most potent inhibitory activity with an IC50 value of 0.63 μM for BRAFV600E and a GI50 value of 0.61 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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| Keywords: | Melanoma Quantitative structure activity relationship (QSAR) Nicotinamide Urea 1H‐Pyrazoles 3 5‐diaryl‐4 5‐dihydro‐ |
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