The first study of the interaction of tin(IV) with the anticancer antibiotic doxorubicin in N,N-dimethylformamide (dmf) solution is reported. Electronic absorption spectroscopy showed that reaction of the drug with SnCl4 is time dependent and involves the initial formation of a 1∶1 complex. The strong binding was also shown by 119Sn NMR spectroscopy. Reactions with modified anthracyclines show that the α-ketol side chain at C9 is essential for interaction, while the quinone chromophore is not involved in binding, as inferred from optical spectroscopy. Proton NMR data suggest that binding to the C9 side chain involves enolization at C13–C14. The two-dimensional total correlation spectra indicate that the daunosamine moiety of doxorubicin can be involved in SnIV binding with formation of several time-dependent species. This was verified by 1H and 119Sn NMR studies of SnIV–daunosaminide hydrochloride systems. These findings suggest that SnIV can bind to doxorubicin at two sites: the C9 α-ketol chain, probably after enolization, and the sugar ring at the 4′-OH and 3′-NH2 positions. This is the first report of metal binding to doxorubicin at the C9 side chain.

Interaction of tin(IV) with doxorubicin / E., Balestrieri; L., Bellugi; A., Boicelli; Giomini, Marcello; A. M., Giuliani; Giustini, Mauro; L., Marciani; P. J., Sadler. - In: JOURNAL OF THE CHEMICAL SOCIETY DALTON TRANSACTIONS. - ISSN 0300-9246. - STAMPA. - 21(1997), pp. 4099-4106. [10.1039/a702588b]

Interaction of tin(IV) with doxorubicin

GIOMINI, Marcello;GIUSTINI, Mauro;
1997

Abstract

The first study of the interaction of tin(IV) with the anticancer antibiotic doxorubicin in N,N-dimethylformamide (dmf) solution is reported. Electronic absorption spectroscopy showed that reaction of the drug with SnCl4 is time dependent and involves the initial formation of a 1∶1 complex. The strong binding was also shown by 119Sn NMR spectroscopy. Reactions with modified anthracyclines show that the α-ketol side chain at C9 is essential for interaction, while the quinone chromophore is not involved in binding, as inferred from optical spectroscopy. Proton NMR data suggest that binding to the C9 side chain involves enolization at C13–C14. The two-dimensional total correlation spectra indicate that the daunosamine moiety of doxorubicin can be involved in SnIV binding with formation of several time-dependent species. This was verified by 1H and 119Sn NMR studies of SnIV–daunosaminide hydrochloride systems. These findings suggest that SnIV can bind to doxorubicin at two sites: the C9 α-ketol chain, probably after enolization, and the sugar ring at the 4′-OH and 3′-NH2 positions. This is the first report of metal binding to doxorubicin at the C9 side chain.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/388270
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