Theoretical investigation of interaction between psoralen and altretamine with stacked DNA base pairs

The present study is an attempt to have a better understanding of physicochemical interaction between anticancer drugs psoralen and altretamine with stacked DNA base pairs. The isolated structural parameters of the stacked base pairs were taken from the Protein Data Bank (PDB) of A-DNA file. The influence of the intercalators on the stability of stacked base pairs was studied based on the results of the interaction energies, which were calculated by the structures of intercalation complexes of psoralen and altretamine with stacked DNA base pairs. The higher dipole moment and polarizability which account for the dispersion forces play an important role during the intercalation of psoralen and altretamine molecules with the base pairs. The stability of the stacking base pairs and their interaction with the intercalator molecules due to the formation of hydrogen bond have been analyzed by Natural Bond Orbital analysis. It has also been noted that intercalator molecules produce significant changes in the values of the phase angle P of pseudorotation conformation of the sugar ring. The physicochemical properties of the psoralen and altretamine as well as the mechanism by which the drug interacts with DNA base pairs allow the rational design of novel anticancer drugs.

Picture showing lowest unoccupied molecular orbital (LUMO) of intercalator interacting complexes at B3LYP/6-31G* level of theory.Figure optionsDownload as PowerPoint slideHighlights
► Psoralen and altretamine drugs were intercalated with stacked DNA base pairs.
► Stability of complexes was studied based on the results of interaction energies.
► High dipole moment and polarization is good candidate for drug design.