Interaction of Anthracycline 3′-azido-epirubicin with Calf Thymus DNA via Spectral and Molecular Modeling Techniques

Anthracycline antibiotics are extensively applied to clinical antitumor therapy. The binding mode and mechanism of a new anthracycline 3′-azido-epirubicin (AEPI) with calf thymus deoxyribonucleic acid (ctDNA) were investigated employing multiple spectroscopy techniques in Tris-HCl buffer solution (pH 7.4). Effect of pH on the interaction was provided to determine the proper environment for whole research. Iodide quenching studies and fluorescence polarization measurement indicated that ctDNA quenched the fluorescence of AEPI significantly via intercalation binding mode. The binding constants and binding sites for the interaction were calculated. From binding constant dependence on the temperature, static quenching mechanism of AEPI by ctDNA was confirmed based on the Stern-Volmer equation. Additionally, the thermodynamic parameters for the reaction revealed that the van der Waals force and hydrogen bonding were the main acting forces in the binding process. Molecular modeling result indicated that the hydrogen bonding played a major role in the binding of AEPI to ctDNA.