Endoplasmic Reticulum (ER)-Targeted Metal-Based Anticancer Chemotherapeutic Agents

In the recent past, an emerging “hot” area of research in medicinal inorganic chemistry that has attracted considerable attention is the design of innovative anticancer metal complexes that target different cellular organelle, and for attaining targeted anticancer drugs aiming at organelles, such as the endoplasmic reticulum (ER), a key organelle responsible for protein, lipid, and hormone synthesis in human cells, there is considerable potential. However, it remains an underexplored therapeutic target. The ER plays a pivotal role in protein folding and cellular detoxification, and when targeted, cellular stress termed as “ER stress” can induce cell death. Despite this significance, synthetic small molecules targeting the ER are scarcely documented in research. The exploration and advancement of metal complexes targeting the ER are still in their early stages. However, there is a tremendous scope for developing new-generation “lead” anticancer agents that mitigate systemic toxicity and drug resistance issues of traditional metal-based drugs and are selective to target cancer cells over noncancerous cells. Based on previous literature reports on structure-activity relationship, some common features of ER-targeting metal complexes are listed here: (1) positively charged, (2) lipophilic nature, and (3) molecular weight > 500 g/mol. In this chapter, we have discussed the recent development in the ER-targeting metal complexes based on recent literature reports with detailed mechanisms of action. The interplay between metal-based drugs and ER stress represents a promising area of research for improving cancer therapies and developing therapeutic strategies that could help to translate these kinds of molecules to clinics.