Viscometric and fluorometric studies of deoxyribonucleic acid interactions of several new anthracyclines.

Abstract

Interactions involved in the binding of the anthracycline analogues adriamycin, carminomycin, pyrromycin, musettamycin, marcellomycin, and aclacinomycin to calf thymus DNA and covalently closed circular PM-2 DNA have been studied. Fluorescence quenching experiments revealed that denaturation of calf thymus DNA and increasing ionic strength each resulted in a marked decrease in the DNA binding affinities of all of the anthracyclines studied. These results suggest that intercalative and electrostatic interactions are both important in the DNA binding of these analogues. Viscometric studies indicated that under high ionic strength conditions which negated electrostatic effects, all of the anthracyclines induced an unwinding--rewinding process of the closed superhelical PM-2 DNA typically observed for DNA intercalators. Relative to the 26 degrees unwinding angle of ethidium bromide, anthracyclines with a daunomycinone-like aglycon induced an unwinding angle of approximately 13 degrees. This differed slightly from the unwinding angles of 10.3 degrees-11.1 degrees which were induced by anthracyclines with a pyrromycinone-like aglycon. Increases in the length of the glycosidic side chain did not elicit significant differences in PM-2 DNA unwinding ability, implying a lack of effect of glycosidic side chain length on the anthracycline intercalation process. The unwinding angles also showed little sensitivity to decreases in ionic strength, suggesting that the fraction of bound anthracycline molecules which are in a nonintercalated state is similar to the fraction of bound ethidium bromide molecules which are in a nonintercalated state.