A bioinorganic approach to face two currently unsolved health issues: food poisoning and cancer

Abstract

This PhD project concerns the study of metal-containing molecules with biological properties and applications. The project has been divided in two different topics: metal complexes with anti-aflatoxigenic activity and metal-based anticancer drugs as alternative to cisplatin. The common thread between the two is the use of thiosemicarbazones, versatile molecules which can be regarded both as biologically active organic molecules by themselves and also as ligands for the synthesis of metal-based drugs. The two topics have been deeply investigated using a multidisciplinary approach which combined chemical and biological experiments. The general workflow we followed consisted in a “hit-to-lead” approach. It started with the identification of promising compounds for our targets from a preliminary screening made on a large group of starting molecules. The work continued using these candidates as lead molecules for the design of a panel of derivatives, which were finally studied in detail to identify the key requirements on which the biological effect was based on and to study the different mechanisms of action. All the results we present are supported both by experimental analysis and computational calculations and many of them were found with the support of a database we built, which was very useful to combine the results that come from different fields.