Small Molecular Probes as Modulators of Targets Involved in Cancer and Neurodegenerative Diseases

Cancer and neurodegenerative diseases represent a great burden on society as they are the leading cause of mortality worldwide, and no adequate therapies are still available today. Thus, the search for promising and innovative new therapies is of paramount importance. This Ph.D. thesis is well inserted in this context since it has the aim of developing small molecules potentially useful for the treatment of cancer and neurodegenerative disorders. For this purpose, four projects have been carried out to develop new potential therapeutics for treating these challenging and widespread diseases. Innovative strategies currently used in medicinal chemistry were exploited, with particular attention to the multitarget-directed ligand (MTDL) approach. More in detail, two series of new compounds targeting adenosine receptors (ARs) and selected carbonic anhydrases (CAs) were developed, respectively for treating glaucoma (Project 1), and as potential anticancer agents (Project 2). Furthermore, two promising targets, the immune checkpoint CD73 and the protein kinase CK1δ, have been taken into account. Inhibitors of these enzymes were designed and synthesized to develop, respectively, novel antitumor agents (Project 3), and compounds potentially useful to treat neurodegenerative disorders, such as ALS (Project 4). The results obtained in the four different projects included in this work could have the potential to fill the still-present therapeutic gaps of these pathologies, providing promising and innovative avenues for the development of novel and effective treatments.