Anthracyclines, metal activation

Beer PD, Bayly SR (2005) Anion Sensing by Metal-Based Receptors. 255 125-162 Beretta GL, Zunino F (2008) Molecular Mechanisms of Anthracycline Activity. 283 1-19 Bergamini G, see Balzani V (2007) 280 1-36 Bergamini G, see Campagna S (2007) 280 117-214... 

Anthracydines have several modes of action leading to anticancer activity. They intercalate between base pairs in DNA, interfering with nucleic acid synthesis. Anthracydines also inhibit DNA topoisomerases I and II, which leads to DNA double-strand breaks. In addition, doxorubicin and daunorubicin may form complexes with metals such as iron. Although these metal-anthracycline complexes result in oxygen free radical formation, which may contribute to antitumor activity, membrane damage incurred from the free radicals is thought to be the mechanism responsible for... 

D. was the first anthracycline to be used clinically in chemotherapy for malignant tumors, however it has strong cardiotoxic side effects. The mechanism of action is complex intercalation into dna, inhibition of topoisomerase II, chelating agent for metal ions such as Fe and Cu, participation in redox reactions, effects on membrane functions. D. also shows anti-Hlv activity. 

Doxorubicin and other anthracyclines, such as daunorubicin, are believed to exhibit their antineoplastic activity through inhibition of topoisomerase II activity. This appears to occur in the absence of significant metal binding by the anthracyclines. Doxorubicin can, however, bind with iron(III) and this results in the formation of a redox-active complex that may cause untoward effects (Myers et al. 1986). Doxorubicin-iron(III) complexes have been shown to oxidatively damage membranes and inactivate protein kinase C, but the biological signficance of this is not well understood (Hannun et al. 1989). 

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