Novel Imidazolyl Derivatives of 1,8-Acridinedione as Potential DNA-Intercalating Agents

The effect of twelve novel imidazolyl derivatives of 1,8-acridinedione (ligands) on calf thymus DNA was studied applying different biophysical techniques including UV-Vis spectrophotometry, CD spectropolarimetry and fluorimetric methods to gain deeper insights into the mechanism of interaction of the ligands with DNA. The binding parameters such as C50, Kapp, ΔGo(H2O) and m-value, followed by Scatchard analysis, indicate that among the tested ligands, four compounds; 12b, 13b, 12f and 13f, containing nitro and benzyl imidazole substituents, revealed uncompetitive intercalative mode of interaction with DNA. UV-Vis studies imply that the compounds bind cooperatively to DNA at the concentration range of 100-200 μM. Based on biophysical data, QSAR analysis, and docking simulations, we propose that in cytotoxic 1,8-acridinediones, the imidazole moiety is essential for pharmacological activity and the introduction of more flexible and electron-withdrawing substituents on the imidazole ring serves to enhance their DNA intercalating ability.