Synthesis, characterization and biological evaluation of new promising copper complexes on different glioblastoma cell lines

Metal complexes, thanks to their biological and chemical diversities, have been the subject of growing interest for years as pharmaceutical agents in cancer diagnostics and therapy. Cisplatin is the most famous metal complex used in cancer therapy. Unfortunately, its use is limited by dose-dependent toxicity and by the onset of drug-resistance phenomena. In this frame, there is urgent need to develop new metal-drugs that act with different mechanisms of action. Anticancer copper-compounds are excellent candidates to substitute platinum-base chemotherapeutics on the basis of the hypothesis that endogenous metals may be less toxic. Copper is involved in many biological pathways and it is an essential element for cellular growth and development. In particular, copper is involved in three typical tumoral pathways: cell proliferation, stimulation of angiogenesis and metastasis. In addition, the concentration of copper in many cancerous tissues is higher than that of normal tissues. In this work, for the preparation of Cu(I) and Cu(II) complexes, the ligand LAd conjugated with the biomolecule 1-adamantylamine has been used. In particular, for the synthesis of Cu(I) complexes the coligands triphenylphosphine (PPh3) and 1,3,5-Triaza-7-phosphaadamantane (PTA) have been employed. For Cu(II) complexes the acceptors copper(II) chlorine and copper(II) bromine have been selected. The antitumoral activity of the new Cu(I) and Cu(II) complexes has been evaluated on U87 and LN18 glioblastoma cell lines by MTT assay. Preliminary results showed that the most promising compounds able to inhibit cancer cell proliferation are those bearing the PPh3 moiety. In order to clarify the mechanisms of cancer cell death induced by the synthetized copper complexes, imaging analyses will be carried out by fluorescence and scanning electron microscopy as well as functional studies (proliferation, cell cycle, cell death marker expression) by flow cytometry.