Sintesi di nuovi inibitori della Topoisomerasi II e della Protocheinchinasi CK2 con potenziale attività antitumorale

The Topoisomerase inhibitors play an essential role in the research of new molecules useful in the antitumor therapy. Topoisomerases are enzymes that regulate the topology of the DNA macromolecule. There are two type of Topoisomeases: Type I are enzymes that cleave single strand of DNA, type II cleaves both strands of DNA and they play an essential role on the cell life. The Topoisomerases are the targets of many antitumor agents currently used in the clinical practice. Proteinkinase CK2 is another interesting target for the potential anti-neoplastic drugs. CK2 is a messenger-indipendent kinase that plays an essential role in cell growth and proliferation. Some studies underline the interaction between Topoisomerase II and proteinkinase CK2 as CK2 is involved in the control of Topo II activity and programmed cell death (apoptosis). The synergism between Topoisomerase II inhibitors and CK2 inhibitors was studied considering that usually the treatment of cancer is a multicomponent therapy. The research was developed with two goals: 1. The synthesis of new Topoisomerase II inhibitors represented by molecular hybrid obtained by functionalization of planar benzoquinazolinic system substituted by methanesulfonamidoanilinic chain of Amsacrine, known drug Topo II inhibitors. 2. The synthesis of new quinolinone proteinkinase CK2 inhibitors and coumarin proteinkinase CK2 inhibitors.