Therapeutic potential of synthetic and natural iron chelators against ferroptosis

Ferroptosis, a regulated form of cell death, is characterized by iron accumulation that results in the production of reactive oxygen species. This further causes lipid peroxidation and damage to the cellular components, eventually culminating into oxidative stress. Recent studies have highlighted the pivotal role of ferroptosis in the pathophysiological development and progression of various diseases such as β-thalassemia, hemochromatosis, and neurodegenerative disorders like AD and PD. Extensive efforts are in progress to understand the molecular mechanisms governing the role of ferroptosis in these conditions, and chelation therapy stands out as a potential approach to mitigate ferroptosis and its related implications in their development. There are currently both synthetic and natural iron chelators that are being researched for their potential as ferroptosis inhibitors. While synthetic chelators are relatively well-established and studied, their short plasma half-life and toxic side effects necessitate the exploration and identification of natural products that can act as efficient and safe iron chelators. In this review, we comprehensively discuss both synthetic and natural iron chelators as potential therapeutic strategies against ferroptosis-induced pathologies. Graphical Abstract: (Figure presented.)