Daunorubicin metallation

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... 

Camptothecin analogs Irinotecan Topotecan Epipodophyllotoxins Etoposide Teniposide Antitumor antibiotics Bleomycin Dactinomycin Daunorubicin Doxorubicin Epirubicin Idarubicin Mitomycin Mitoxantrone Valrubicin Microtubule agents Docetaxel Paclitaxel Vinblastine Vincristine Vinorelbine Enzymes Asparaginase Pegasparaginase Metals... 

Daunorubicin hydrochloride (daunomycin hydrochloride) is an anthracycline antibiotic that inhibits cellular proliferation by a variety of mechanisms, including DNA binding, free radical formation, membrane binding, and metal-ion chelation (49). A number of studies examining efficacy and toxicity in an animal model of PVR have been performed (50-56). Prior to 1998, experience with daunorubicin in human trials was more limited (57-59). 

Hartmann KI, Nieto A, Wu EC, Freeman WR, Kim JS, Chhablani J, Sailor MJ, Cheng L (2013) Hydrosilylated porous silicon particles function as an intravitreal dmg dehvery system for daunorubicin. J Ocul Pharmacol Then doi 10.1089/jop.2012.0205 Holland JM, Stewart MP, Allen MJ, Buriak JM (1999) Metal mediated reactions of porous silicon surfaces. J Solid State Chem 147 251-258... 

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). 

Fig. 7.3. Structures of the metal binding antibiotics adriamycin (doxorubicin), R = CH3 (74), daunorubicin, R = H (74) and streptonigrin (75).

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