Development of ebsulfur analogues as potent antibacterials against methicillin-resistant Staphylococcus aureus

Huy X. Ngo, Sanjib K. Shrestha, Keith D. Green, Sylvie Garneau-Tsodikova

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Antibiotic resistance is a worldwide problem that needs to be addressed. Staphylococcus aureus is one of the dangerous “ESKAPE” pathogens that rapidly evolve and evade many current FDA-approved antibiotics. Thus, there is an urgent need for new anti-MRSA compounds. Ebselen (also known as 2-phenyl-1,2-benzisoselenazol-3(2H)-one) has shown promising activity in clinical trials for cerebral ischemia, bipolar disorder, and noise-induced hearing loss. Recently, there has been a renewed interest in exploring the antibacterial properties of ebselen. In this study, we synthesized an ebselen-inspired library of 33 compounds where the selenium atom has been replaced by sulfur (ebsulfur derivatives) and evaluated them against a panel of drug-sensitive and drug-resistant S. aureus and non-S. aureus strains. Within our library, we identified three outstanding analogues with potent activity against all S. aureus strains tested (MIC values mostly ⩽2 μg/mL), and numerous additional ones with overall very good to good antibacterial activity (1–7.8 μg/mL). We also characterized the time-kill analysis, anti-biofilm ability, hemolytic activity, mammalian cytotoxicity, membrane-disruption ability, and reactive oxygen species (ROS) production of some of these analogues.

Original languageEnglish
Pages (from-to)6298-6306
Number of pages9
JournalBioorganic and Medicinal Chemistry
Issue number24
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd


  • Antibiotic
  • Benzisothiazolinone
  • Biofilm
  • Reactive oxygen species (ROS)
  • Resistance

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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