Zur Interaktion von Anthracyclinen und Anthracyclinonen mit DNS / Interaction of Anthracyclines and Anthracyclinones with DNA

Abstract

It was shown by the polarographic data of the complexes between antracycline antibiotics and DNA that in contrast to their biological inactive aglycones and other antracyclinones, a cooperative interaction of the intercalating chromophore as well as the sugar residue of the anthracycline molecules, is generally responsible for the complex formation with DNA. The high complex binding constants of the antracyclines daunomycin, nogalamycin, galirubin A and galirubin B measured in dimethylsulfoxid-buffer solution are in the same order of magnitude as those of actinomycins. On the other hand, only a weak binding ability of the aglycones daunomycinon, ε-pyrromycinon and aklavinon, as well as of other investigated anthracyclinones and model hydroxyanthraquinones, could be observed. No significant influence of the number and positions of the chromophore hydroxyls could be noticed. The results suggest that the first outerphase addition of the sugar residues to the backbone of the helix gives the necessary space of time for the slower intercalation process of the planar chromophore. In the case of denatured DNA, the antibiotic-DNA-complex has a lowered stability. The important role of the sugar residue for the binding mechanism strongly suggests that modifications of the nature and position of the basic sugar residue should be most valuable for the synthesis of new effective anthracyclines.