Boron-containing compounds for medical applications

This thesis discusses the development - syntheses and preliminary biological tests – of new potential boron delivery agents for Boron Neutron Capture Therapy (BNCT) and boron-containing drug analogs. Chapter 1 and Chapter 2 describe the main project of the thesis concerning the synthesis of boron-delivery agents for a BNCT guided by Positron Emission Tomography (PET). Pairing the BNCT with a suitable imaging technique could considerably increase the efficacy and applicability of the therapy. We conceived our target molecules as typical theranostic agents: a carbohydrate moiety for cellular targeting and a trifluoroborate group as the active part for BNCT and PET. Chapter 1 details the synthesis and subsequent biological studies performed on trifluoroboratesstabilized by internal ammonium salts. Chapter 2 describes a second family of glycoconjugates containing sulfonium ions instead of ammonium. From the data collected from the first class of compounds, we decided to move toward molecules bearing the trifluoroborates stabilized by internal sulfonium salts to improve their stability. Chapter 3 focuses on a small side project steamed from the collaboration between the University of Milan, the University of Firenze, and the University of Pavia, concerning the synthesis of a nanomaterial decorated with boranes. Chapter 4 explains the synthetic efforts made to obtain a carborane analog of aproxen, well-known non-steroidal anti-inflammatory drug. This project has been part of a broader effort ongoing in the Hey-Hawkins’s laboratory to perform isosteric substitutions of aromatic rings in common drug scaffolds with inorganic structures, such as carboranes.