Synthesis and biological evaluation of 3,5-diaryl-pyrazole derivatives as potential antiprostate cancer agents

Prostate cancer is the most frequently diagnosed tumor in men and the second leading cause of cancer-associated mortality in most developed countries. 3,5-Diaryl substituted pyrazole derivatives (20–28) were prepared starting from related chalcones and biologically evaluated for in vitro growth inhibition activity against PC3 and DU145 human prostate cancer cell lines. Compounds 23, 26, and 28 were found to be more potent as compared to the other halogen-substituted derivatives. Especially, the 2-bromo-substituted pyrazole derivative (26) was found to be more potent against PC3 and DU145 cells. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) are known to be expressed in DU145 and PC3 cancer cells. The binding mode of the most selective compound 26 toward EGFR and VEGFR2 was investigated by employing docking simulations based on GLIDE standard precision (−5.912 and −6.949 kcal/mol, respectively).