Coumarins as modulators of ferroptosis across cancer, neurodegeneration, and cardiovascular disorders
- 1Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq
Abstract
Background: Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation and oxidative stress. It has emerged as a key contributor to the pathophysiology of cancer, neurodegenerative disorders, and cardiovascular diseases. Coumarins, a diverse class of benzopyrone-derived compounds, exhibit antioxidant, pro-oxidant, and iron-chelating properties, suggesting their potential role in modulating ferroptotic pathways. Aim: This review aims to systematically evaluate the role of certain coumarins as modulators of ferroptosis and to explore their therapeutic implications across major disease contexts. Methods: A comprehensive literature analysis was conducted focusing on experimental and preclinical studies investigating the interaction between coumarins and ferroptosis-related mechanisms, including iron metabolism, lipid peroxidation, and antioxidant defense systems such as the GPX4/GSH axis. Results: Available preclinical evidence indicates that coumarins exert dual regulatory effects on ferroptosis. In in vitro and limited in vivo cancer models, several derivatives promote ferroptotic cell death through GPX4 inhibition, increased lipid peroxidation, and disruption of system Xc − activity. Conversely, in preclinical neuronal and cardiovascular systems, coumarins exhibit protective effects in vitro and in vivo by enhancing antioxidant defenses, activating Nrf2 signaling, and maintaining redox balance. These context-dependent actions are closely linked to structural diversity and pharmacokinetic properties of the compounds. Conclusion: Coumarins represent promising, yet underexplored, modulators of ferroptosis. However, clinical translation is currently restricted by major barriers, including low bioavailability and other pharmacokinetic challenges, a complete lack of direct clinical evidence, and the absence of standardized ferroptosis assessment methods. Addressing these limitations through robust in vivo validation is essential to clarify their therapeutic applicability.
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BibTeX
@article{mustafa2026coumarins,
title = {{Coumarins as modulators of ferroptosis across cancer, neurodegeneration, and cardiovascular disorders}},
author = {Yasser Fakri Mustafa},
journal = {Advances in Biomarker Sciences and Technology},
year = {2026},
month = nov,
doi = {10.1016/j.abst.2026.10.001},
url = {https://doi.org/10.1016/j.abst.2026.10.001},
note = {CC BY},
}
RIS
TY - JOUR
TI - Coumarins as modulators of ferroptosis across cancer, neurodegeneration, and cardiovascular disorders
AU - Yasser Fakri Mustafa
PY - 2026
DA - 2026/11/01
JO - Advances in Biomarker Sciences and Technology
DO - 10.1016/j.abst.2026.10.001
UR - https://doi.org/10.1016/j.abst.2026.10.001
AB - Background: Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation and oxidative stress. It has emerged as a key contributor to the pathophysiology of cancer, neurodegenerative disorders, and cardiovascular diseases. Coumarins, a diverse class of benzopyrone-derived compounds, exhibit antioxidant, pro-oxidant, and iron-chelating properties, suggesting their potential role in modulating ferroptotic pathways. Aim: This review aims to systematically evaluate the role of certain coumarins as modulators of ferroptosis and to explore their therapeutic implications across major disease contexts. Methods: A comprehensive literature analysis was conducted focusing on experimental and preclinical studies investigating the interaction between coumarins and ferroptosis-related mechanisms, including iron metabolism, lipid peroxidation, and antioxidant defense systems such as the GPX4/GSH axis. Results: Available preclinical evidence indicates that coumarins exert dual regulatory effects on ferroptosis. In in vitro and limited in vivo cancer models, several derivatives promote ferroptotic cell death through GPX4 inhibition, increased lipid peroxidation, and disruption of system Xc − activity. Conversely, in preclinical neuronal and cardiovascular systems, coumarins exhibit protective effects in vitro and in vivo by enhancing antioxidant defenses, activating Nrf2 signaling, and maintaining redox balance. These context-dependent actions are closely linked to structural diversity and pharmacokinetic properties of the compounds. Conclusion: Coumarins represent promising, yet underexplored, modulators of ferroptosis. However, clinical translation is currently restricted by major barriers, including low bioavailability and other pharmacokinetic challenges, a complete lack of direct clinical evidence, and the absence of standardized ferroptosis assessment methods. Addressing these limitations through robust in vivo validation is essential to clarify their therapeutic applicability.
SN - 2543-1064
ER -