Design, Synthesis and Biological Evaluation of Pyrazole derivatives as Potential multikinase Inhibitors in Hepatocarcinoma.

We described the optimization, by molecular modelling, of small pyrazole derivatives, obtained through a 1,3-dipolar cycloaddition between nitrile imines and functionalized acetylenes. The two kinase inhibitors, selected as potential agents active against hepatocellular carcinoma (HCC) were then evaluated in vitro for their biological activity on HCC-derived cell lines. The compounds show an inhibitory growth efficacy (IC50 50–100 M) in SNU449 cell line, as well as block of cell cycle progression and induction of apoptosis, and can be considered as lead compounds for further SAR developments