New approaches to anticancer therapy through different targets

Throughout my three years as a Phd student I have worked on several projects, mostly concerning research and development of new anticancer drugs. The wider project concerned the development of a new chemotherapy agent as inhibitor of tubulin polymerization. My research group has significant experience in this field, so we decided to continue this study focusing on the need to overcome problems such as drug resistance and poor bioavailability. Starting from derivatives previously reported, we made structural modifications to implement pharmacodynamic and pharmacokinetic properties. The results of cell tests on these novel inhibitors showed significant activity in many cell lines which showed resistance to approved drug. In vivo studies have also highlighted the efficiency of some derivatives onbrain tumors such as glioblastoma. Many traditional drugs, fail to effectively cross epithelial and cellular barriers, which reduces their effectiveness and requires high dosages. This novel tubulin polymerization inhibitors have instead a better pharmacokinetic profile, proving to be able to cross the blood-brain barrier. Another aim of my PhD project was to search for new targets for cancer therapy. A widespread problem is the poor selectivity of the classic chemotherapeutic compounds, which is able to inhibit the proliferation of cancer cells, but shows certain degree cytotoxicity also towards normal cells. Anticancer therapy is, therefore, increasingly focused on new specific cancer targets. In this context we have developed new inhibitors of β-catenin, Gab2 and carbonic anhydrase. Finally, I also took part in two smaller projects in the antiviral field. Starting from docking studies, we developed possible antiviral agents active against Norovirus or Zikavirus