Interaction of metal complexes with DNA and proteins: towards a new generation of therapeutic and imaging agents

The search for new chemicals that have therapeutic properties is a lengthy and costly process that continuously looks for chemical diversity. While organic compounds have been extensively studied in this context far less is known about the therapeutic properties of metal complexes. In spite of the great success of some metallo-pharmaceuticals such as cis-platin in cancer therapy, and gadolinium complexes in Magnetic Resonance Imaging (MRI), medicinal inorganic chemistry has received comparatively very little attention from the pharmaceutical industry and in general from the medicinal chemistry community. However, the structural and electronic versatility of metal centres provide a unique opportunity to explore chemical diversity for the rational design of drugs. Furthermore, metals often have attractive optical and magnetic properties that are ideally suited for the development of molecular probes for bio-imaging. The project herein presented aims at developing novel metal complexes as potential anticancer drugs. In particular, we will aim to develop complexes that can selectively interact with a specific type of DNA (named quadruplex DNA which in recent years has been increasingly associated with regulatory processes in the human genome and has emerged as a novel and distinctive target for the development of anticancer drugs). To realize the full therapeutic potential of the compounds developed, their interactions with proteins relevant to transport and delivery will be studied. Besides the potential therapeutic properties of the compounds developed (with the obvious implications to a range of beneficiaries) we will also aim to develop molecular probes that can be used to gain a better understanding of the interaction of small molecules and quadruplex DNA.Metal-containing compounds have been overlooked for a long time by the pharmaceutical industry and medicinal chemistry community. However, their distinctive structural and functional properties provide a unique opportunity for the development of new therapeutic agents and imaging tools. The vision of this project is to demonstrate that metal complexes that interact with quadruplex DNA, can be excellent candidates for the development of anticancer drugs and also unique probes for bio-imaging.