Design, Synthesis and Biological Evaluation of Novel Chemical Entities as Potential Anticancer Drugs and for the Control of the Metastatic Process

The coordination chemistry of poly(pyrazolyl)alkanes has been extensively developed with particular interest arising out of the versatility of this class of ligands such as the ease of modifying the steric and electronic environment about the metal center by variation of the azolyl moiety or the substituents on the azolyl groups. Recently new nitroimidazole conjugated heteroscorpionate ligands, namely LMN and LMN1, were synthesized by direct coupling of preformed side chain acid and amine components. The related copper(II) complexes {[(LMN)2Cu]Cl2} and {[(LMN1)2Cu]Cl2} have been prepared and evaluated for their cytotoxic activity towards a panel of several human tumour cell lines. To evaluate the antimetastatic activity of the copper complexes tumour cell invasion tests and PTP1B inhibition assays are in progress. We have also designed a new heteroscorpionate ligand by coupling reaction of the bis(3,5-dimetil-pyrazolil)alkane with a selective I1-receptor agonist endowed with antiproliferative activity on PC12 cell lines (LI1) and we are studying its coordination ability towards copper(I)/(II) acceptors.