Degradation of Anthracycline Antitumor Compounds Catalysed by Metal Ions

Fiallo, Marina; Haj, Hayet Tayeb-Bel; Garnier‐Suillerot, Arlette

doi:10.1155/mbd.1994.183

Cited by 5 publications

(9 citation statements)

References 8 publications

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“…These observations should help to understand the interactions of anthracycline with metal ions, in particular to determine the coordination site of the molecule involved in these interactions. 39 Recently 2D 1 H NMR spectroscopy (EXSY and COSY) has been proposed as a powerful technique in studying the interaction between anthracyclines and metal ions. 40 In this report, we have shown that CD spectroscopy can give precise information on the structure of these systems, with the advantage to use less concentrated solutions and to require less time in recording the spectra.…”

Section: Resultsmentioning

confidence: 99%

Circular Dichroism Studies on Anthracycline Antitumor Compounds. Relationship between the Molecular Structure and the Spectroscopic Data

Fiallo¹,

Tayeb²,

Suarato³

et al. 1998

Journal of Pharmaceutical Sciences

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The band assignment of the circular dichroism (CD) spectra of anthracyclines can provide us with the tools to study the interaction of these molecules with biomolecules, such as DNA and membranes, and also with metal ions. This paper reports the CD spectra of 17 anthracycline derivatives and the tentative assignment of the bands to specific electronic transitions. The deprotonation of some anthracyclines, such as doxorubicin, daunorubicin, and idarubicin, have been also studied in order to characterize the electronic transitions involved in the acid-base process. Our evidence suggests the following assignment. The position of the band assigned to pi-->pi transition, polarized along the short axis of the molecule ( approximately 290 nm), does not depend on the hydroxyl group at C(11) (presence and/or ionization state), whereas the position of the band assigned to the pi-->pi transition ( approximately 480 nm), polarized along the long axis, is strongly dependent on it. Concerning the n-->pi transitions, the bands at approximately 320 and approximately 350 nm have a strong contribution of the n-->pi C(12)=O transition and the n-->pi C(5)=O transition, respectively.

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Section: Resultsmentioning

confidence: 99%

Circular Dichroism Studies on Anthracycline Antitumor Compounds. Relationship between the Molecular Structure and the Spectroscopic Data

Fiallo¹,

Tayeb²,

Suarato³

et al. 1998

Journal of Pharmaceutical Sciences

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“…The formation of the Fe 3+ -doxorubicin complexes elicited broad absorption bands centered at 600 nm (see the ESI †), as previously reported. 63,66,67 Experiments with Fe(III)-doxorubicin proved problematic due to drifting electrode measurements, formation and precipitation of Fe(OH) 3 as well as low concentrations of complex formed under the experimental conditions utilized. Despite the apparent distance between the amino group and the iron binding site of doxorubicin, the charge on the amino group is known to influence the strength of interaction with the metal ion.…”

Section: Stability Constantsmentioning

confidence: 99%

Iron(iii)-binding of the anticancer agents doxorubicin and vosaroxin

et al. 2015

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The Fe(iii)-binding constant of vosaroxin, an anticancer quinolone derivative, has been determined spectrophotometrically and compared with the analogous Fe(iii) complex formed with doxorubicin. The in vivo metabolic stability and iron coordination properties of the quinolones compared to the anthracylines may provide significant benefit to cardiovascular safety. The mechanism of action of both molecules target the topoisomerase II enzyme. Both doxorubicin (Hdox, log βFeL3 = 33.41, pM = 17.0) and vosaroxin (Hvox, log βFeL3 = 33.80(3), pM = 15.9) bind iron(iii) with comparable strength; at physiological pH however, [Fe(vox)3] is the predominant species in contrast to a mixture of species observed for the Fe:dox system. Iron(iii) nitrate and gallium(iii) nitrate at a 1 : 3 ratio with vosaroxin formed stable tris(vosaroxacino)-iron(iii) and tris(vosaroxino)gallium(iii) complexes that were isolated and characterized. Their redox behavior was studied by CV, and their stereochemistry was further explored in temperature dependent (1)H NMR studies. The molecular pharmacology of their interaction with iron(iii) may be one possible differentiation in the safety profile of quinolones compared to anthracyclines in relation to cardiotoxicity.

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“…For instance, the ferric complex of daunorubicin (Dnr) retains its biological properties, 5 whereas the one of doxorubicin (Dox) does not. 12 In the latter case the metal ion coordination leads to considerable ligand degradation, 6,13 which is not the case with the free ligand kept under similar experimental conditions. [14][15][16] Within the last two decades, several papers concerning the interaction between Fe 3+ and anthracycline derivatives have been published.…”

Section: Introductionmentioning

confidence: 98%

“…18 Afterward, on the grounds of electronic absorption spectroscopy studies, [19][20][21] Fe 3+ was generally accepted to form a major complex in which the metal ion binds three anthracycline molecules. Magnetic susceptibility measurements have shown the coordination of six oxygen atoms 20 to Fe 3+ and the metal ion binding site has been generally assumed to be located on the {C (12)dO; C(11)-O -} functions. 22 This binding preference, according to Myers, 23 was derived from better fitting of the distance between the oxygens of this site and Fe 3+ .…”

Section: Introductionmentioning

confidence: 99%

Solution Structure of Iron(III)−Anthracycline Complexes

et al. 1999

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The interaction of Fe(3+) with the anthracycline anticancer drug idarubicin (Ida) was studied by absorption, CD, Mössbauer, and EPR spectroscopy. The formation of two major Fe(3+)-Ida complexes, labeled I and II, was observed. In complex I, Fe(3+) ion was bound to anthracycline at the {C(12)=O; C(11)-O(-)} coordination site. In complex II, two Fe(3+) ions were bound at sites {C(5)=O; C(6)-O(-)} and {C(12)=O; C(11)-O(-)}, respectively. Complex I was an equimolar monomeric species with a 1:1 Fe(3+):Ida stoichiometry (beta(1) = 4.8 x 10(11) M(-1)), whereas in complex II the anthracycline ligand was bridging two metal ions, alternatively bound to both anthracycline ring chelating sites with the assumption that the ratio of Fe(3+):Ida in complex II was 2:1 (beta(2) = 5.3 x 10(24) M(-2)). Alternatively, complex II may be oligomeric with Fe(3+):Ida = 1:1 and with each Fe(3+) bridging two Ida molecules. Our findings could be important in understanding the biological effects of the anthracycline-ferric complexes. Thus, providing information about the nature of the Fe(3+)-Ida system, we suggest that the formal 1:3 Fe(3+):anthracycline complexes, reported in the previous literature, could be a mixture of species I, II, and free ligand.

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Degradation of Anthracycline Antitumor Compounds Catalysed by Metal Ions

Cited by 5 publications

References 8 publications

Circular Dichroism Studies on Anthracycline Antitumor Compounds. Relationship between the Molecular Structure and the Spectroscopic Data

Circular Dichroism Studies on Anthracycline Antitumor Compounds. Relationship between the Molecular Structure and the Spectroscopic Data

Iron(iii)-binding of the anticancer agents doxorubicin and vosaroxin

Solution Structure of Iron(III)−Anthracycline Complexes

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