Gold(I) N-Heterocyclic Carbene Complexes  : a Chemical and Biological Study of Therapeutic Potential as New Anticancer Agents

The following PhD thesis dealt with gold(I) N-heterocyclic carbene complexes as innovative anticancer agents. The initial drug design was based on the chemical properties and bioactivity of a recent potent gold phosphol inhibitor: GoPI. A first series of complexes was synthesized and intensively biological investigated. Features such as the inhibition of enzymes of the antioxidant network (e.g. thioredoxin reductase), reactive oxygen species stimulation and apoptosis induction were observed. Moreover, the gold(I) complexes demonstrated an antiproliferative potential in the range of established anticancer drugs. Based on the results of the biological investigation, other two structure activity relationship series were synthesized and tested. A rational improvement in cytotoxic activity was observed. The chemical environment at the gold atom proved to be a key feature to achieve a specific bioactivity. Overall, the results contributed to explain and characterized the biological profile of the gold(I) N-heterocyclic carbene complexes class.