Siderophore-Mediated Disruption of Ferroptosis in Pyricularia oryzae: A Novel Strategy for Rice Blast Control

Rice (Oryza sativa L.) is the staple food for more than half of the global population. Among its diseases, rice blast—caused by Pyricularia oryzae—is the most destructive, resulting in estimated yield losses of 20–40% worldwide. Management of this disease depends largely on intensive fungicide use, accounting for over 8% of the global fungicide market.1 Over time, multiple classes of fungicides have been used to control P. oryzae,2,3 including strobilurins and demethylation inhibitors (DMIs).4 Although, these compounds primarily act on single molecular targets, which has led to the gradual emergence of resistant pathogen populations. As a result, there is an urgent need to identify new molecular targets and develop innovative chemical scaffolds for more effective disease management. In this context, modulation of ferroptosis—a recently described form of iron-dependent regulated cell death—has emerged as a promising strategy to disrupt fungal pathogenicity. In P. oryzae, ferroptosis is initiated in the terminal conidial cell and then propagates to the remaining two cells during appressorium formation and maturation, a process essential for successful host infection. Notably, ferric ions (Fe3+), rather than ferrous ions (Fe2+), play a critical role in triggering ferroptosis in this pathogen.5 Here, we describe the synthesis and biological evaluation of natural and nature-inspired catecholamide-based iron chelators (siderophores) as potential modulators of ferroptosis in P. oryzae (Figure 1).