Intercalation of anticancer drug mitoxantrone into DNA: Studied by spectral and surface plasmon resonance methods

Abstract

Studying DNA interaction with different drugs is interesting and important in discovering the interaction mechanism and developing novel drugs. Mitoxantrone (MTX) is a potent antitumor drug used to treat certain types of cancer. In this work, we evaluated the binding strength of MTX to 16 base pair double strands (ds) DNA. For the first time, this work investigates the intercalation of anticancer drugs into DNA by spectral fluorescence spectroscopy and SPR (surface plasmon resonance) based methods. Furthermore, the thermodynamic and kinetic parameters, including KD, KA, entropy change (ΔS), enthalpy change (ΔH), and ΔG, were calculated using different concentrations of ds DNA at three different temperatures. The results indicated that MTX binding to DNA was an exothermic and spontaneous process. The negative value of both ΔH and ΔS calculated by SPR and fluorescence data analysis showed that hydrogen bonding was the major binding force for the complexation of MTX to DNA. In addition, fluorescence data analysis revealed that MTX could quench the DNA fluorescence via the static quenching mechanism. This study shows that the investigation of intercalation anticancer drugs into DNA can be studied by spectral methods and can be investigated using SPR based method, and obtained data from the SPR method is as reliable as the fluorescence method. The present work shows hydrogen bonding is the major binding force in intercalating MTX to DNA.