The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations.

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Mazerski J, Martelli S, Borowski E

The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: molecular dynamics simulations.

Acta Biochim Pol. 1998;45(1):1-11.

PubMed ID

9701490 [ View in PubMed

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Abstract

Intercalative binding of the antitumor drugs ametantrone and mitoxantrone to the dodecamer duplex d(CGCGAGCTCGCG)2 was studied by applying molecular dynamics in water with the GROMOS 87 force field. A number of reasonable binding orientations were tested by short pre-simulations. It was shown that in energetically favourable orientation the anthraquinone chromophore is perpendicular to the direction of inter-base hydrogen bonds. Helically shaped side-chains of the drugs fit to the minor groove. The best orientation obtained in pre-simulations was applied in the main simulations. Small but significant differences were found between structures of intercalation complexes of the two drugs with the dodecamer duplex, the mitoxantrone complex possessing more favourable energy. The molecular nature of interactions responsible for those differences has been discussed.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mitoxantrone	DNA	Nucleotide	Humans	Yes	Intercalation	Details