Landscaping DNA binding potential of piperine derivatives by computational and biophysical methods

Piperine, the alkaloid from Black pepper, is known for its wide range of pharmacological effects. The DNA binding activity of piperine was reported earlier. In this work, we explore the DNA duplex binding properties of four piperine derivatives, piperonal, piperonyl alcohol, piperonylic acid, and piperic acid using biophysical and computational techniques. Various spectroscopic and calorimetric techniques were employed for the experimental analysis. We employed UV - vis absorption and fluorescence spectroscopy to verify the binding of piperine to calf thymus DNA (ctDNA). The energetics of this interaction were analysed using isothermal titration calorimetry (ITC). Conformational changes in DNA resulting from ligand interactions were investigated using circular dichroism spectroscopy. All these experimental results consistently demonstrate that the piperine derivatives exhibit stronger binding affinity to DNA than piperine. Computational analyses, utilizing molecular docking and dynamics, revealed similar results to experimental studies, indicating that the compounds bind to the minor groove of DNA like piperine. Both in vitro and in silico investigations demonstrated the strong DNA binding potential of the examined piperine derivatives. This study is the first to report on the comparative interaction between these piperine derivatives and a DNA duplex.