Antiproliferative activities of procainamide and its binding with calf thymus DNA through multi-spectroscopic and computational approaches

The interaction between procainamide with ct-DNA was seen through several experimental and theoretical methods. The fluorescence intensity of procainamide decreased on increasing the concentration of ct-DNA and the quenching process was found to be static with approximately 1:1 binding between ct-DNA and procainamide. UV absorption spectroscopy gave an idea about minor groove binding which was further confirmed by the dye displacement method of DAPI/EtBr bounded ct-DNA interaction. Minor groove binding was also evidenced from the collective information obtained from DNA melting, viscosity and CD spectroscopy. Molecular docking simulations presented that procainamide bound in the minor groove (AT rich) region of B-DNA structures. From thermodynamic point of view the binding interaction between procainamide and ct-DNA was spontaneous process with liberation of energy and overall ordering of system. Hydrogen bonding was found to play important role as suggested by the values of thermodynamic parameters. Whereas from molecular docking simulations it was exposed that hydrogen bonding and hydrophobic interactions were crucial in the binding of ct-DNA and procainamide. DFT method was also used to calculate the Frontier molecular orbitals (HOMO and LUMO) of procainamide which were further used to calculate chemical potential (mu), chemical hardness (q) and fraction number of electrons (Delta N) from procainamide to DNA. Procainamide was found to act as electron donor to DNA bases excpet guanine. Finally, elucidation of anticancer activity revealed that procainamide possesses potential cytotoxicity against MCF-7 breast cancer cells and able to induce significant level of apoptosis at concentrations below IC50 value. (C) 2018 Elsevier B.V. All rights reserved.