6533b85afe1ef96bd12b89a8

RESEARCH PRODUCT

Model building and molecular mechanics calculations of mitoxantrone-deoxytetranucleotide complexes: Molecular foundations of DNA intercalation as cytostatic active principle

subject

description

Several intercalation complexes of the antitumor-active drug mitoxantrone with base paired tetranucleotides were constructed by molecular modeling using computer graphics and molecular mechanics calculations. The mitoxantrone molecule favours DNA binding into CG intercalation site. The two side chains of the drug are orientated into the major groove and fixed by hydrogen bonds with the nucleotide bases. This molecular study can be helpful for understanding the mode of action of cytostatically active compounds and to design new structurally related compounds of the anthraquinone drug type.