Influence of some chromophore substituents on the intercalation of anthracycline antibiotics into DNA

The interaction between some chromopore-modified daunorubicin derivatives and calf thymus DNA was studied using a number of physical techniques in order to investigate the effect substituents on the aromatic ring system have on the capacity to intercalate into DNA and on the DNA binding affinity. The modifications examined include methylation of the hydroxyl groups at the 6 and 11 positions of the B ring and removal of the 11-hydroxyl group. The studies showed that only 11-deoxydaunorubicin retains the ability to bind to DNA by the intercalation mechanism typical of the parent compound, although the structural modification leads to an appreciably weaker binding. In contrast, methylation of any hydroxyl group dramatically reduces the affinity of the drug for DNA. At physiological ionic strength both methyl ether derivatives showed no evidence of intercalation. Structure activity correlations for the intercalation reaction deduced from these studies are in agreement with earlier findings and hypotheses relating to antitumour activity.