Investigations of drug–DNA interactions using molecular docking, cyclic voltammetry and UV–Vis spectroscopy

Molecular docking and QSAR studies were carried out for the investigation of interactions between 11 antitumor drugs and double stranded DNA. Quantitative structure activity relationship was established using MOE software package showing good correlation of binding strength with various physicochemical parameters e.g., hydrophobic surface area (Vsurf), EHOMO, EHUMO, partition coefficient (log P) and molar refractivity (MR) of the drugs.The most important parameter obtained from the docking studies was the formation constant (Kf) which is an indicative of the binding strength of the drug with DNA. This parameter was also calculated using the experimental techniques namely cyclic voltammetry (CV) and UV–Vis spectrophotometry. Variation in electrochemical characteristics (shift in peak potential and peak current decrease) and spectral profile of these drugs on the addition of DNA were used to determine the values of formation constant. The docking studies were used to predict the mode of interaction of the drug with DNA. It was observed that as far as binding strength was concerned the computational results complemented the experimental results. The order of magnitude of experimental and theoretical Kf was same. The high value of Kf implied that the respective drugs bind to DNA most efficiently.

► Experimentally obtained and theoretically predicted Kf have same order of magnitude.
► Binding strength of yet to be synthesized compounds can be predicted.
► The EHOMO and steric descriptors exhibited an inverse and direct relation with Kf.
► Molecular docking methods provided the visual representation of the phenomenon.
► In some cases mixed mode of interaction was predicted theoretically.