Characterization of interaction of calf thymus DNA with gefitinib: Spectroscopic methods and molecular docking

• Gefitinib binds to ct-DNA via minor groove binding and forms 1:1 complex with it.
• The main interaction forces were van der Waals and hydrogen bonding interactions.
• There was slight change of the conformation of ct-DNA due to binding gefitinib.
• The flexibility of gefitinib plays an important role in increasing the gefitinib–ct-DNA stability.

The binding interaction of gefitinib with calf thymus DNA (ct-DNA) under the simulated physiological pH condition was studied employing UV absorption, fluorescence, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results revealed that gefitinib preferred to bind to the minor groove of ct-DNA with the binding constant (Kb) of 1.29 × 104 L mol−1 at 298 K. Base on the signs and magnitudes of the enthalpy change (ΔH0 = −60.4 kJ mol−1) and entropy change (ΔS0 = −124.7 J mol−1 K−1) in the binding process and the results of molecular docking, it can be concluded that the main interaction forces between gefitinib and ct-DNA in the binding process were van der Waals force and hydrogen bonding interaction. The results of CD experiments revealed that gefitinib did not disturb native B-conformation of ct-DNA. And, the significant change in the conformation of gefitinib in gefitinib–ct-DNA complex was observed from the molecular docking results and the change was close relation with the structure of B-DNA fragments, indicating that the flexibility of gefitinib molecule also plays an important role in the formation of the stable gefitinib–ct-DNA complex.

It has been confirmed that gefitinib interacts with ct-DNA via minor groove binding mode through spectroscopic methods (such as UV–vis absorption spectroscopy, fluorescence emission spectroscopy) and molecular doching.Figure optionsDownload as PowerPoint slide