A multifaceted approach towards organometallic anticancer agent development
Christian G. Hartinger
Abstract
The approaches taken to develop novel metal-based anticancer agents have considerably changed over the last 50 years since the discovery of the platinum drugs and focus now on compounds that interact with proteins overexpressed in tumor cells, show novel modes of DNA interactions or accumulate with higher selectivity in tumors, to name a few. The structural diversity of anticancer agents has steadily increased and organometallic compounds are widely investigated. Over the years, bioorganometallic chemistry has developed into the thriving field of research it is today and in particular the development of anticancer agents with bioactive co-ligands coordinated to the metal center has received a lot of attention. In this personal perspective, I discuss concepts we use in anticancer metallodrug design and metallomics strategies to interrogate their modes of action. I focus on the impact of ligand structures on the biological activity of their organometallic complexes, complemented by observations of unexpected reactions and surprising behavior in the presence of biomolecules.