Synthesis of 3,5-Bis(trifluoromethyl)phenyl-Substituted Pyrazole Derivatives as Potent Growth Inhibitors of Drug-Resistant Bacteria

Molecules. 2021 Aug 22;26(16):5083. doi: 10.3390/molecules26165083.

Abstract

Enterococci and methicillin-resistant S. aureus (MRSA) are among the menacing bacterial pathogens. Novel antibiotics are urgently needed to tackle these antibiotic-resistant bacterial infections. This article reports the design, synthesis, and antimicrobial studies of 30 novel pyrazole derivatives. Most of the synthesized compounds are potent growth inhibitors of planktonic Gram-positive bacteria with minimum inhibitory concertation (MIC) values as low as 0.25 µg/mL. Further studies led to the discovery of several lead compounds, which are bactericidal and potent against MRSA persisters. Compounds 11, 28, and 29 are potent against S. aureus biofilms with minimum biofilm eradication concentration (MBEC) values as low as 1 µg/mL.

Keywords: Enterococcus faecalis; Enterococcus faecium; MRSA; Staphylococcus aureus; VRE; aniline; pyrazole.

MeSH terms

  • Bacteria / drug effects
  • Bacteria / growth & development*
  • Biofilms / drug effects
  • Cell Death / drug effects
  • Drug Resistance, Bacterial / drug effects*
  • Enterococcus faecalis / drug effects
  • Enterococcus faecalis / physiology
  • Growth Inhibitors / chemical synthesis*
  • Growth Inhibitors / chemistry
  • Growth Inhibitors / pharmacology*
  • HEK293 Cells
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / physiology
  • Microbial Sensitivity Tests
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*

Substances

  • 3,5-bis(trifluoromethyl)pyrazolate
  • Growth Inhibitors
  • Pyrazoles