Unraveling the coptisine–ctDNA binding mechanism by multispectroscopic, electrochemical and molecular docking methods

Abstract

Coptisine, an isoquinoline alkaloid, is an important medicinal herbal extract with diverse pharmacological and biological activities. Based on these considerations, an explorative study of the interaction of coptisine with calf thymus DNA (ctDNA) was conducted using multispectroscopic, electrochemical and molecular modeling techniques under simulative physiological conditions. Absorption spectra and iodide quenching experiments indicated that intercalation was the main DNA binding mode for coptisine. Fluorescence studies revealed that this interaction process is predominantly a dynamic process. This was further confirmed in a difference absorption spectrum and in electrochemical studies. The apparent activation energy, E_a, remained largely constant at different temperatures. DNA chemical denaturation was used to further investigate the interaction and provided further support for the intercalation. Furthermore, CD spectroscopy confirmed that coptisine not only interacted with the ctDNA, but it also perturbed ctDNA structure. In addition to experimental approaches, molecular modeling was used as a tool to verify and expand the experimental outcomes.