Design, synthesis, DNA binding, and biological activity of a series of DNA minor-groove-binding intercalating drugs.

A group of pseudopeptides, molecular combination of the natural antitumor agents distamycin or netropsin and the anilinoacridine chromophore (which is related to the synthetic antileukemic drug amsacrine) has been synthesized. Their DNA binding properties were determined and discussed in terms of their structural differences and in relation to their observed base-dependent binding. Binding data are consistent with a model in which the acridine nucleus occupies an intercalation site and the netropsin or distamycin residue resides in the DNA minor groove. Cytostatic and cytotoxic activities against a murine cell line are reported, as well as significant differences in the inhibition of DNA synthesis.