title: Iron(III)-adriamycin and Iron(III)-daunorubicin complexes: physicochemical characteristics, interaction with DNA, and antitumor activity.
abstract: Fe(III) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric and spectroscopic measurements, we have shown that adriamycin and daunorubicin form two well-defined species with Fe(III), which can be formulated as respectively Fe(HAd)3 and Fe(HDr)3. In these formulas, HAd and HDr stand for adriamycin and daunorubicin in which the 1,4-dihydroxy-anthraquinone moiety is half-deprotonated. Both complexes are six-membered chelates. The stability constant is beta = (2.5 +/- 0.5) X 10(28) for both complexes. Interaction with DNA has been studied showing that, despite strong coordination to Fe(III), anthracyclines are able to intercalate between DNA bases pairs, releasing the metal. These complexes display antitumor activity against P 388 leukemia that compares with that of the free drug. Fe(HAd)3, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase. Moreover, it is shown that the triferric adriamycin compound so called "quelamycin" is in fact a mixture of Fe(HAd)3 and polymeric ferric hydroxide.
authors.forename: H
authors.initials: H
authors.lastname: Beraldo
authors.forename: A
authors.initials: A
authors.lastname: Garnier-Suillerot
authors.forename: L
authors.initials: L
authors.lastname: Tosi
authors.forename: F
authors.initials: F
authors.lastname: Lavelle
mesh_terms: D002942:Circular Dichroism; D004247:DNA; D003630:Daunorubicin; D004317:Doxorubicin; D005290:Ferric Compounds; D007364:Intercalating Agents; D007501:Iron; D009245:NADH Dehydrogenase / Q000378:metabolism; D013057:Spectrum Analysis; D013059:Spectrum Analysis, Raman; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000096:biosynthesis
chemical_list: D005290:Ferric Compounds; D007364:Intercalating Agents; D013481:Superoxides; D004317:Doxorubicin; D004247:DNA; D007501:Iron; D009245:NADH Dehydrogenase; D003630:Daunorubicin