Abstract

The interactions of synthetic and natural anthracyclines were studied by determination of binding constants to calf thymus DNA using spectrophotometric titration and thermal denaturation of drug-DNA solutions to determine the Tm values. The two ways of evaluation of DNA-drug interaction showed reasonable correlation. In particular, the glycosides with non-natural aglycones or major structural deviation showed consistently lower binding constants and Tm values. In the case of daunorubicin and 4-demethoxydaunorubicin these data also correlated reasonably with antitumor efficacy. However, in other instances, there were many deviations and a direct simple correlation between binding parameters and biological activity can not be established.

Keywords: DNA-drug binding constants, Anthraquinone, Daunosamine glycosides, DNA, Intercalation, Thermal denaturation, Melting points Tm