1. Design, Synthesis and Biological Evaluation of Pyrazole derivatives as Potential multikinase Inhibitors in Hepatocarcinoma
- Author
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Mauro Comes-Franchini, Francesca Fornari, Carlo Maurizio Camaggi, Simone Breviglieri, Manuela Minguzzi, Maddalena Milazzo, Valentina Rebuttini, Erica Locatelli, Laura Gramantieri, Luigi Bolondi, Elena Strocchi, F. Fornari, M. Minguzzi, E. Strocchi, E. Locatelli, L. Gramantieri, M. Milazzo, V. Rebuttini, S. Breviglieri, C. M. Camaggi, L. Bolondi, and M. Comes Franchini
- Subjects
Models, Molecular ,Spectrometry, Mass, Electrospray Ionization ,Carcinoma, Hepatocellular ,Magnetic Resonance Spectroscopy ,Nitrile ,Blotting, Western ,Antineoplastic Agents ,Pyrazole ,Molecular Dynamics Simulation ,molecular docking, kinase inhibitors ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Protein Kinase Inhibitors ,Cell Proliferation ,Pharmacology ,Binding Sites ,Chemistry ,Kinase ,Organic Chemistry ,Liver Neoplasms ,Biological activity ,General Medicine ,hepatocellular carcinoma ,medicine.disease ,Cycloaddition ,pyrazole ,Biochemistry ,dipolar cycloaddition ,Cell culture ,Apoptosis ,Hepatocellular carcinoma ,Pyrazoles ,Protein Kinases - Abstract
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 (IC 50 50–100 μM) 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.
- Published
- 2012