COUMARIN-BASED COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE AND CANCER

The goal of this PhD project was to identify small molecules for the treatment of Alzheimer’s disease (AD) and cancer, two of the most significant challenges in modern medicine. The research encompassed several approaches. The main line of research employed a structure-based strategy for designing coumarin-based inhibitors of cholinesterases (ChEs) and monoamine oxidase B (MAO B), key enzymes to the pathogenesis of AD. These compounds were evaluated for in vitro potency and preliminary drug-like properties. The PhD project also explored the development of coumarin-based inhibitors of monoamine oxidase A (MAO A), given the emerging role of MAO in cancer therapy. Furthermore, with the aim of discovering multi-target-directed small molecules for AD and cancer, previously identified compounds with diverse scaffolds active against various relevant targets (e.g., MMPs, MAOs, ChEs) were evaluated for their activity on adenosine receptor subtypes (A1, A2A, A2B, A3) using a cell-based assay. This focus was driven by the involvement of adenosine receptors in the pathophysiology of both AD and cancer. These investigations have exploited the potential of coumarin-based derivatives as versatile therapeutic agents.