Halogenation of Biotin Protein Ligase Inhibitors Improves Whole Cell Activity against Staphylococcus aureus

ACS Infect Dis. 2018 Feb 9;4(2):175-184. doi: 10.1021/acsinfecdis.7b00134. Epub 2017 Nov 16.

Abstract

We report the synthesis and evaluation of 5-halogenated-1,2,3-triazoles as inhibitors of biotin protein ligase from Staphylococcus aureus. The halogenated compounds exhibit significantly improved antibacterial activity over their nonhalogenated counterparts. Importantly, the 5-fluoro-1,2,3-triazole compound 4c displays antibacterial activity against S. aureus ATCC49775 with a minimum inhibitory concentration (MIC) of 8 μg/mL.

Keywords: Staphylococcus aureus; antibiotic; biotin protein ligase; enzyme inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Binding Sites
  • Biotin / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Halogenation
  • Humans
  • Ligases / antagonists & inhibitors*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Protein Binding
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology*

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Biotin
  • Ligases