Thiazolidinone-isatin hybrids as multi-target anticancer agents

During the three years of PhD two main projects have been carried out. The projects were focused on the design, synthesis, and characterization of small molecules with antitumoral activity. Cancer is one of major causes of death in the world and, considering its multi-factorial origin it could be considered more a syndrome than a disease. Accordingly, in most cases the treatment consists of a combination of drugs that, due to their lack of selectivity and toxicity are often used at sub-optimal concentrations and scheduled in cycles. Thus, drug resistance and comorbidity, are among the main obstacles in cancer treatment, making the therapy less effective. Therefore, the need for new drugs and treatments is urgent. In particular, the first project is focused on human carbonic anhydrase IX and XII, two targets that are present and consistently validated as markers of disease progression in hypoxic solid tumours. Therefore, considering that isatin and thiazolidinone could be considered as privileged scaffolds in medicinal chemistry and pursuing in our ongoing work on benzene sulphonamides isatin-thiazolidinone hybrids as inhibitors of hCA IX and hCA XII, four series of molecules were successfully synthesized and characterized. Biochemical tests performed on hCA I, hCA II, hCA IX, and hCA XII isoforms have shown promising results on the selectivity and activity of these new derivatives. Since the isatin scaffold contains some of the pharmacophoric features of FDA approved kinase inhibitors, including Sunitinib and Nintedanib, the second project aims to the design and synthesis of indolinone derivates able to inhibit different kinases. In this respect, I have been visiting researcher at the University College Cork, in Ireland, under the supervision of Dr. Florence McCarthy, where I investigated synthetic approaches to obtain bis-indole derivatives.