Novel amino-pyrazole analogues interfering with cell migration

5-pyrazolyl urea derivatives represent attractive molecules endowed with interesting pharmaceutical properties. In particular, GeGe-3 showed promising antiangiogenetic activity interfering with MAPK and PI3K signalling pathways and inhibiting proliferation and migration in HUVEC cells. Furthermore, proteomic studies indicated Calreticulin as potential target for this derivative. To further extend the structure-activity relationships of GeGe-3, a novel series of amino pyrazoles was designed and synthesized. The adopted synthetic strategy led to the formation of new amino pyrazoles 2 and their carbamate analogues 3. All the new derivatives were preliminary tested in MTT assay to evaluate their antiproliferative activity on a panel of tumour and normal cell lines. A Western Blot screening was carried out to assess the compounds’ ability to interfere with AKT and ERK1/2 phosphorylation. Moreover, cell proliferation and cell migration tests highlighted interesting antiangiogenetic properties for the prepared compounds. Interestingly, selected compounds, proved to be more effective than GeGe-3, designated as reference compound. The synthetic procedures, the structural elucidation as well as the biological properties of the prepared pyrazoles will be discussed in the presentation.