Design, synthesis and biological evaluation of pyrazole derivatives as potential multi-kinase inhibitors in hepatocellular carcinoma

作者：Strocchi Elena; Fornari Francesca; Minguzzi Manuela; Gramantieri Laura; Milazzo Maddalena; Rebuttini Valentina; Breviglieri Simone; Camaggi Carlo Maurizio; Locatelli Erica; Bolondi Luigi; Comes Franchini Mauro^*

来源：European Journal of Medicinal Chemistry, 2012, 48: 391-401.

DOI：10.1016/j.ejmech.2011.12.031

• Pyrazole
• Dipolar cycloaddition
• Hepatocellular carcinoma
• Molecular docking
• Kinase inhibitors

We described the optimization, by molecular modelling, of small pyrazole derivatives, as kinase inhibitors, obtained through a 1,3-dipolar cycloaddition between nitrile imines and functionalized acetylenes. The two compounds, 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 a promising inhibitory growth efficacy (IC50 50-100 mu 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.

• 出版日期2012-2