Biochemical Mechanistic Pathway of Cell Death Induced by Metal-Based Chemotherapeutic Agents

A large plethora of metal complexes that could act as potent anticancer chemotherapeutic agents have been designed and developed in the recent past using innovative design strategies based on ligand scaffolds and central core metal ions. Although these metal-based drug entities have been comprehensively studied based on their preliminary interactions with the most likely therapeutic targets such as DNA, RNAs, and proteins, their binding affinities, modes, and cleaving abilities are determined by biophysical methods, quantifying various parameters that reveal interactions in varying strength from low borderline to high. The in vitro cytotoxicity profile has been validated on a panel of cancer cell lines including resistant cancer cells. There is, however, scarce in vivo cytotoxicity and genotoxicity data available for most of the designed drug candidates that limit their passage to further clinical trials. Despite the fact these metal-based drug entities are potent, they fail at R&D levels or do not reach clinical trials. Therefore, it seems imperative to understand and unravel the biochemical mechanistic pathway of cell death induced by metal-based chemotherapeutics. In this chapter, we present the biochemical mechanistic pathway induced by these metal-based complexes containing different metal ions and myriad ligand topologies. The added subtitle Apoptosis and Role of ROS and Glutathione further highlights their significance in cell inhibition pathways and also guides the readers to the journey of deciphering the most active “therapeutic” compounds via these mediators.