Computational studies on G-quadruplex DNA-stabilizing property of novel Wittig-based Schiff-Base ligands and their copper(II) complexes

A series of mono imine (C=N) group that contained Wittig-based Schiff-Base ligands was optimized using the DFT-based computational method and Gaussian 09 program package. These optimized molecules were docked with Quadruplex DNA (PDB ID: 1KF1) and duplex DNA (PDB ID: 1BNA) using AutoDock Vina program along with the reference molecules. Schiff-Base ligands derived from fused aromatic rings contained amines and precursor aldehyde (PA-5 both Z and E isomers) showed lower binding energy for G-quadruplex DNA among all and N-5 category both Z and E isomer Schiff-Base ligands have shown high selectivity for G-quadruplex DNA over duplex DNA which is a very important phenomenon to develop the G-quadruplex DNA stabilizers. For a few Schiff-Base molecules like Ligand-6 ( 1-{[2-Hydroxy-5-(2-pyren-1-yl-vinyl)-benzylidene]-amino}-naphthalen-2-ol ) of N-5 category both Z and E isomers with groove binding and end stacking modes, molecular dynamic calculations were carried out. The study revealed that Ligand-6 of N-5 category E isomer with groove binding mode has higher stabilizing effect on G-quadruplex DNA in spite of having the higher binding energy value. Among Schiff-Base copper(II) complexes, Complex-3 ( E-(1-{[2-Hydroxy-5-(2-pyren-1-yl-vinyl)-benzylidene]-amino}-naphthalen-2-ol)Cu ) is having high binding affinity for G-quadruplex DNA as compared to others.