Interaction of deoxyribonucleic acid with anthracenedione derivatives

Spectrophotometric, calorimetric and chrioptical techniques have been used to investigate the interaction of two new anthracenedione derivatives, 1-(ω-diethylaminopropylamido)-4-hydroxy-9,10-anthracenedione hydrochloride (I) and 1-(ω)-diethylaminopropylamido)-2-methoxy-4-hydroxy-9,10-anthracenedione hydrochloride (II) to DNA. Measurements were carried out at four different Na⁺ concenetrations. From the dependence of the binding constant on ionic strength the number of ion pairs formed between the ligand and DNA, along with the binding free energy were estimated. Calorimetric measurements show that the binding process is exothermic for both ligands. Experiments carried out with DNA from various sources indicate no marked preference for G-C or A-T binding sites. Compounds I and II increase the T_m for DNA melting by more than 25°C at high drug/base pair ratios. Circular dichroism studies indicate that the structural properties of DNA are substantially affected by the interaction with the above mentioned compounds. All data from these studies are consistent with an intercalative mechanism of binding for the anthracendione derivatives to DNA.