Interaction of tacrine-coumarin derivatives with double stranded DNA: spectroscopic and molecular docking study

Identifying the ways in which drugs interact with DNA is crucial from a pharmacological point of view, and therefore determining the binding mode of tacrine-coumarin derivatives with DNA is key to gaining a fuller understanding of the activity of these compounds. Seven tacrine-coumarin derivatives 1a-1d and 2a-2c have been evaluated for their binding affinity to calf thymus DNA (ctDNA) by a variety of spectroscopic techniques including UV-Vis absorbance, fluorescence and CD spectroscopy. The effect of 1a-1d and 2a-2c on thermal denaturation profiles of ctDNA was also studied. The binding constants for the ctDNA-drug complexes were determined on the basis of spectrophotometric and spectrofluorometric titrations. Evidence has been provided that the tacrine-coumarin hybrid molecules bind to ctDNA through a non-intercalative mode of interaction such as groove binding. For derivatives 1d and 2c molecular docking was performed for two different DNA conformations. The results of preliminary molecular docking show that the most favourable DNA binding mode of these derivatives is non-intercalative.

Automated summary

Identifying the binding mode of tacrine-coumarin derivatives with DNA is essential for understanding their pharmacological activity. This study evaluated the binding affinity of seven derivatives to ctDNA using various spectroscopic techniques and determined that they bind through a non-intercalative groove binding mode. Molecular docking results further confirmed the non-intercalative DNA binding mode for two specific derivatives.