DNA sequence preferences for the anti-cancer drug mitoxanthrone and related anthraquinones revealed by DNase I footprinting.
The interaction has been studied of several anthraquinone-based intercalating drugs, including the anti-cancer agent mitoxantrone, with defined sites of DNA. A 160 base pair DNA sequence from tyrT was employed for footprinting with DNase I. The anthraquinones had aminoalkylamino substituents in various positions of the ring system. Inhibition of enzymatic cutting of the DNA was observed at various positions on the sequence, mostly around some of the pyrimidine-3',5'-purine sites. Enhancements to cutting were observed clustered around AT-rich regions. The compounds showed differences in detailed footprinting behaviour, which have been related to differences in their mode of interaction with DNA as found in earlier computer modelling studies.
D000880:Anthraquinones / Q000494:pharmacology*; D001483:Base Sequence; D004247:DNA / Q000032:analysis*; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D007364:Intercalating Agents / Q000494:pharmacology*; D008942:Mitoxantrone; D013329:Structure-Activity Relationship
D000880:Anthraquinones; D007364:Intercalating Agents; D004247:DNA; D008942:Mitoxantrone; D003850:Deoxyribonuclease I