Anthracycline-iron complex

Anthracycline-iron complexes are chemical coordination complexes formed by the binding of iron ions (Fe2+ or Fe3+) to the hydroxyquinone and carbonyl groups of anthracycline drugs, such as doxorubicin and daunorubicin [2, 7]. These complexes are central to the 'iron-and-free-radical' hypothesis of anthracycline-induced cardiotoxicity, which remains a major dose-limiting factor in cancer chemotherapy [1, 3]. Within the heart, these complexes act as potent catalysts for the Fenton and Haber-Weiss reactions, facilitating the production of highly reactive hydroxyl radicals from superoxide and hydrogen peroxide [3, 5]. The resulting oxidative stress leads to lipid peroxidation of mitochondrial membranes, protein oxidation, and DNA damage, ultimately causing irreversible cardiomyocyte death and congestive heart failure [2, 4]. The cardioprotective drug dexrazoxane works by chelating iron and preventing the formation of these toxic complexes, thereby reducing the risk of cardiac damage without compromising the antitumor efficacy of the anthracyclines [1, 10].

Other names

Iron-anthracycline complexFerric-anthracycline complexDoxorubicin-iron complexFe(III)-anthracycline complex

Iron chelation and inhibition of reactive oxygen species generation