MODEL-BUILDING AND MOLECULAR MECHANICS CALCULATIONS OF MITOXANTRONE-DEOXYTETRANUCLEOTIDE COMPLEXES - MOLECULAR FOUNDATIONS OF DNA INTERCALATION AS CYTOSTATIC ACTIVE PRINCIPLE

Several intercalation complexes of the antitumor-active drug mitoxantr one with base paired tetranucleotides were constructed by molecular mo deling using computer graphics and molecular mechanics calculations. T he mitoxantrone molecule favours DNA binding into CG intercalation sit e. The two side chains of the drug are orientated into the major groov e and fixed by hydrogen bonds with the nucleotide bases. This molecula r study can be helpful for understanding the mode of action of cytosta tically active compounds and to design new structurally related compou nds of the anthraquinone drug type.