Kinetics of the DNA binding of 2-substituted anthraquinones.

The DNA-binding properties of the 2-substituted-1,4-dihydroxyanthraquinones 5-12 were examined. Compounds 5 and 6 were synthesized in this study, 7-12 were already available. Spectral studies were consistent with intercalation of 5, 6 and 8 into DNA. Affinity constants were in the range of 3 x 10(4)M-1. Compounds 7 and 10-12 showed no DNA binding, presumably being sterically excluded from binding. The kinetics of the DNA interaction of 5, 6 and 8 were studied. There is a biphasic process. This may reflect an initial reaction, with drug from this first mode of binding moving into the second binding mode (a sequential process) or independent binding of drug in two sets of sites (a parallel process). The methods used in this study do not allow us to discriminate between these models. However, if the parallel binding model is correct, the compounds show sequence selectivity of binding, and provide a lead for further development of neutral DNA-binding ligands with sequence selectivity.