The clinically useful anticancer drug mitoxantrone intercalates prefer
entially into 5'-(A/T)CG and 5'-(A/T)CA sites on DNA. The 5,8 hydroxyl
substituents on its anthracenedione chromophore are available to inte
ract with the double helix. Footprinting experiments with two anthraqu
inone derivatives structurally related to mitoxantrone and ametantrone
have been undertaken to assess the influence of the hydroxyl groups o
n the DNA recognition process. The results confirm that they do play a
role in the recognition of preferred nucleotide sequences and suggest
that the binding of anthraquinones to a 5'-(A/T)CG site is dependent
on the presence of the 5,8 hydroxyl substituents whereas binding to 5'
-(A/T)CA sites appears to proceed just as well without them.