Theoretical investigation of interaction between Gatifloxacin and DNA: Implications for anticancer drug design

Abstract

This study is an attempt to have a better understanding of the physicochemical interaction between a novel anticancer drug, Gatifloxacin (GTFX) and its biological receptor, DNA. The eventual purpose is to design drugs which interact more with DNA. Considering the physicochemical properties of the drug as well as the mechanism by which it interacts with DNA, it should eventually allow the rational design of novel anticancer or antiviral drugs. Molecular modeling on the complex formed between Gatifloxacin and DNA presented the full ability of the drug for participating in the formation of a stable intercalation site. Besides, the molecular geometries of Gatifloxacin (GTFX) and the DNA bases (Adenine, Guanine, Cytosine and Thymine) were optimized with the aid of B3LYP/6-31G⁎ method. The properties of the isolated intercalator and its stacking interactions with the adenine⋯thymine (AT) and guanine⋯cytosine (GC) nucleic acid base pairs, were studied using DFTB method, (an approximate version of the DFT method) that was extended to cover the London dispersion energy. The B3LYP/6-31G⁎ stabilization energies of the intercalator⋯base pair complexes were found to be − 26.99 and − 37.62 kcal/mol for AT⋯GTFX and GC⋯GTFX, respectively. It was completed that the dispersion energy and the electrostatic interaction contributed to the stability of the intercalator⋯DNA base pair complexes.