An in-silico analysis reveals 7,7'-bializarin as a promising DNA gyrase B inhibitor on Gram-positive and Gram-negative bacteria

Abstract

Bacterial diseases are considered by the World Health Organization to be one of the greatest threats to public health worldwide, mainly due to the increasingly frequent resistance to traditional antibiotics. Estimates from the World Bank indicate that the annual global economic impacts of antibiotic resistance will reach US$1.0-3.4 trillion by 2030. With this, the demand for studies aiming at the discovery of new antibiotics or molecules that may play a synergistic role within the spectrum of drug-resistant bacteria is of fundamental importance. In this in silico study, ligands generated from anthraquinones with established antibacterial activity were evaluated as potential inhibitors of the DNA gyrase subunit B of two species of Gram-positive and two Gram-negative bacteria. The main result of molecular docking-based virtual screening reveals several anthraquinones with remarkable binding energies, of which 7,7'-bializarin (ZINC000004783172) exhibited the highest value for all DNA gyrases subunit B studied and formed stable complexes, as evidenced by molecular dynamics simulations. Collectively, the results presented here reveal the potential of this molecule to bind tightly to the active site of DNA gyrases subunit B of Escherichia coli, Salmonella enterica (subtype typhi), Enterococcus faecalis, and Staphylococcus aureus, and therefore represents a promising candidate for further in vitro testing aimed at evaluating its antibacterial effect.

Keywords: 7,7′-bializarin; Anthraquinones; DNA gyrase B; Enterococcus faecalis; Escherichia coli; Gram-negative; Gram-positive; Molecular dynamics simulation; Salmonella enterica subtype Typhi; Staphylococcus aureus, molecular docking.