A quinoline-based FtsZ inhibitor for the study of antimicrobial activity and synergistic effects with β-lactam antibiotics

J Pharmacol Sci. 2018 Jul;137(3):283-289. doi: 10.1016/j.jphs.2018.07.005. Epub 2018 Jul 17.

Abstract

The antibacterial activity and the synergistic effect with β-lactam antibiotics of a new 1-methylquinolinium iodide derivative were investigated. The experimental results indicate that the compound possesses a strong antibacterial activity against a panel of bacteria including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and NDM-1 Escherichia coli with the MIC values from 0.75 μg/mL to 6 μg/mL. In addition, this compound combined with β-lactam antibiotics shows strong synergistic antimicrobial activities against antibiotic-resistant strains of S. aureus. The results of biochemical studies also reveal that this compound can effectively disrupt GTPase activity, polymerization of FtsZ, and cell division to cause cell death. The compound shows high potential for further development as a new generation of antibacterial agents to fight against the emergence of multidrug-resistant bacteria.

Keywords: Antibacterial activity; Bacterial resistance; Cell division; FtsZ inhibitor; Synergistic effect.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Cell Division / drug effects
  • Cytoskeletal Proteins / antagonists & inhibitors*
  • Cytoskeletal Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Drug Resistance, Bacterial
  • Drug Synergism
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology
  • GTP Phosphohydrolases / metabolism
  • Methicillin-Resistant Staphylococcus aureus / cytology
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Polymerization / drug effects
  • Quinolinium Compounds / pharmacology*
  • Vancomycin-Resistant Enterococci / drug effects*
  • beta-Lactamases
  • beta-Lactams / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria
  • Quinolinium Compounds
  • beta-Lactams
  • 1-methylquinolinium
  • beta-Lactamases
  • beta-lactamase NDM-1
  • GTP Phosphohydrolases