Abstract

The DNA binding characteristics of the new anthracycline antitumor antibiotics, marcellomycin and rudolfomycin, were compared with those of their respective 10-descarbomethoxy analogues. The fluorescence spectra were determined and the fluorescence quenching effects caused by interactions with the four natural DNAs—calf thymus DNA, salmon sperm DNA, Clostridium perfringens DNA and Micrococcus luteus DNA—were characterized. Binding parameters were determined by Scatchard analyses of results obtained by titrating anthracycline fluorescence with increasing concentrations of DNA. Removal of the carbomethoxy-group from position 10 of marcellomycin or rudolfomycin caused a significant reduction in DNA binding ability for all four DNAs studied. These results are correlated with a marked decrease in antitumor activity, and nucleolar RNA synthesis inhibitory activity, as previously reported, and thus confirm earlier studies indicating that one subcellular target of anthracycline antitumor action is nucleolar preribosomal RNA synthesis. Additionally, the correlation between DNA binding ability and antitumor activity provides further evidence of the mechanism of action of Class II anthracyclines.