Interaction of Natural and Synthetic Anthracyclines with DNA (Supporting Material)

Karsten      Krohn

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