Design, synthesis and biological characteristics of pyrazolo[3,4-]pyrimidine derivatives as potential VEGFR-2 inhibitors.

Several VEGFR-2 inhibitors with the structure of [3,4-d]pyrimidine and based on sorafenib were designed and synthesized. Cytotoxic activity was evaluated by MTT, wound healing and clone formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Molecular simulation and western blot were also applied. Among them, significantly inhibited tumor cellular activity (IC = 5.90 ± 0.05 μM on HepG2 cells) compared with sorafenib (IC = 9.05 ± 0.54 μM on HepG2 cells). Molecular docking demonstrated that and sorafenib have the same hydrogen binding. Finally, the protein expression of phosphorylated VEGFR-2 was substantially reduced after treatment. Compound can inhibit VEFGR-2 activation and is an effective antitumor agent in liver cancer cells.