DNA RECOGNITION BY 2 MITOXANTRONE ANALOGS - INFLUENCE OF THE HYDROXYL-GROUPS

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.