Studies of anthracycline--DNA complexes by circular dichroism.
A series of doxorubicin and daunorubicin analogues have been investigated in aqueous solution and as DNA-bound forms by means of circular dichroism (c.d.) spectroscopy. The structural variants comprise modifications on the amino sugar, on the aliphatic ring and the side chain of the aglycone moiety, and of the substitution pattern of the anthraquinone chromophore. Results with compounds having conformational constraints interfering with optimal fitting to DNA indicate that stereochemistry and conformation of the aliphatic ring predominantly affect c.d. spectra of anthracyclines in DNA-bound as well as in free form. Conformational correspondence with the known structure of the daunorubicin-oligonucleotide complex is inferred from the spectra of derivatives with modifications at position 6 or 11 in the anthraquinone chromophore. On the other hand, a different binding geometry is postulated for compounds either lacking the 4-methoxy group of daunorubicin (idarubicin and derivatives) or having a phenolic function in its place (carminomycin and derivatives). A possible relation with cytotoxic activity is discussed at a speculative level.
Rizzo
V
V
Farmitalia Carlo Erba, Research & Development, Milan, Italy.
Penco
S
S
Menozzi
M
M
Geroni
C
C
Vigevani
A
A
Arcamone
F
F
D000903:Antibiotics, Antineoplastic; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008968:Molecular Conformation; D009279:Naphthacenes / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D004317:Doxorubicin; D004247:DNA; D003630:Daunorubicin