Design, synthesis and biological evaluation of novel 5-amino pyrazoles with antiangiogenic properties

The pyrazolyl urea GeGe-3 was identified as a potential angiogenesis inhibitor, interfering with MAPK and PI3K signaling pathways in HUVEC cells. The compound was able to inhibit cell migration and proliferation and to interfere with the intersegmental tube formation in zebrafish embryos. Furthermore, other investigation led to the identification of DMPK1 and Calreticulin as potential target of the derivative. To further extend the structure-activity relationships of GeGe-3, a new series of amino pyrazoles were designed and synthesized, leading to the isolation of highly functionalized pyrazoles 2 and their carbamate analogues 3. All the derivatives were preliminary screened for their antiproliferative activity by MTT assay on a panel of tumor and normal cells line. Moreover, Western Blot analysis, cell proliferation and cell migration studies were carried out and selected compounds showed interesting antiangiogenetic properties.