Cancer is a leading cause of death worldwide. Nowadays, the treatment of cancer by chemotherapy can consist of a combination of antitumor drugs. Nevertheless, chemotherapy is accompanied by serious side effects and intrinsic and acquired resistance to the drugs. This thesis describes the design and synthesis of novel potential antitumor drugs that combine two different mechanisms of action. One of the two active units is derived from cisplatin, which cured Lance Armstrong?s testicular cancer. This platinum compound is known to induce a distortion of the DNA helix upon binding, resulting in the death of the cancer cells. The second active moiety is based on Cu(3-Clip-Phen), which is a highly active nuclease agent. In other words, the platinum moiety act as an antitumor drug and as an anchor to DNA, while the copper unit cleaves the DNA strand in the close proximity of the platinum-DNA adducts. The two active units have been covalently coupled with a (in)flexible bridge aiming at a synergistic action of the two drugs. The cleaving activity of some of the complexes is higher compared to Cu(3-Clip-Phen). Moreover, three of the new complexes have been found to show equivalent or higher cytotoxicities compared to cisplatin or Cu(3-Clip-Phen).UBL - phd migration 201
