Synthesis, molecular modeling, DNA binding, and antitumor properties of some substituted amidoanthraquinones

A series of 1- and 1,4-substituted amidoanthraquinones have been prepared, with side chains possessing basic nitrogen atoms. Computer modeling and energy calculations have shown that all eight compounds can bind intercalatively to DNA and that there are significant differences in the additional nonbonded and electrostatic interactions possible at the DNA binding site. Solution DNA binding and closed-circular DNA unwinding studies confirmed intercalative interactions, and the predicted differences in strength of interactions between mono- and disubstituted compounds were found. All compounds were modestly cytotoxic to L1210 cells in culture. In vivo activity against L1210 and S180 tumors was not found for the monosubstituted compounds, whereas the four disubstituted ones had varying levels of measurable, though low, activity.