Naphtho[1,2-b]furan-4,5-dione is a potent anti-MRSA agent against planktonic, biofilm and intracellular bacteria

Future Microbiol. 2017 Sep:12:1059-1073. doi: 10.2217/fmb-2017-0044. Epub 2017 Aug 11.

Abstract

Aim: Naphtho[1,2-b]furan-4,5-dione (N12D) and naphtho[2,3-b]furan-4,9-dione (N23D) are furanonaphthoquinone derivatives from natural resources. We examined the antimicrobial activity of N12D and N23D against drug-resistant Staphylococcus aureus.

Materials & methods: Minimum inhibitory concentration, minimum bactericidal concentration, bacterial viability and agar diffusion assay were conducted against methicillin-resistant S. aureus (MRSA) and clinical isolates of vancomycin-resistant S. aureus.

Results & conclusion: The minimum inhibitory concentration of N12D and N23D against MRSA was 4.9-9.8 and 39 μM, respectively. With regard to the agar diffusion test, the inhibition zone of the quinone compounds was threefold larger than that of oxacillin. N12D was found to inhibit MRSA biofilm thickness from 24 to 16 μm as observed by confocal microscopy. N12D showed a significant reduction of the intracellular MRSA burden without decreasing the macrophage viability. The antibacterial mechanisms of N12D may be bacterial wall/membrane damage and disturbance of gluconeogenesis and the tricarboxylic acid cycle.

Keywords: MRSA; biofilm; molecular docking; proteomics; quinone.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / drug effects
  • Biofilms / drug effects*
  • Cell Membrane / drug effects
  • Cell Survival / drug effects
  • Citric Acid Cycle
  • Furans / chemistry
  • Furans / pharmacology
  • Gluconeogenesis / drug effects
  • Humans
  • Keratinocytes / drug effects
  • Macrophages / drug effects
  • Methicillin-Resistant Staphylococcus aureus / cytology
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Microscopy, Electron, Transmission
  • Molecular Docking Simulation
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology*
  • Neutrophils / drug effects
  • Oxacillin / pharmacology
  • Proteomics
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects
  • Vancomycin Resistance

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Furans
  • Naphthoquinones
  • naphtho(1,2-b)furan-4,5-dione
  • Oxacillin