DESIGN AND SYNTHESIS OF NOVEL ZINC-DEPENDENT METALLOENZYMES INHIBITORS AS ANTI-TUMORAL DRUG CANDIDATES.

Cancer is a wide diffuse pathology, many can be the causes such as genetic predisposition, environmental, diet and life-style. Several treatment exist in order to avoid or cure cancer, but unfortunately, no one of these can lead to total healing. Matrix metalloproteinases are a family of zinc dependent enzyme, there are plenty experimental evidence that an over expression of these enzymes are correleated in cancer. Their inhibition seems to be a good weapon for fight some kind of cancer. In this PhD thesis are reported the inhibitors which have been synthesized under the advice of computational chemist of university of Napoli. Ubiquitin-proteasome is another complex system which is involved in cancer, especially in breast. BCA2, an E3 enzyme is over-express in 57% of aggressive breast cancer and among E2 enzymes, Ubc5Hb seems to be involved in apoptosis and cancer invasiveness. Computational studies mada by Cardiff Uni (Cardiff, Wales, UK) have given as result disulfiram analogue and triazinic based scaffold as inhibitor for these enzymes. Here we report synthesis and optimization.