Structure-activity relationships of pyrazole-4-carbodithioates as antibacterials against methicillin–resistant Staphylococcus aureus

Hiwa Majed, Tatiana Johnston, Celine Kelso, Enrico Monachino, Slobodan Jergic, Nicholas E. Dixon, Eleftherios Mylonakis, Michael J. Kelso

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious hospital-acquired infections and is responsible for significant morbidity and mortality in residential care facilities. New agents against MRSA are needed to combat rising resistance to current antibiotics. We recently reported 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) as a new bacteriostatic agent against MRSA that appears to act via a novel mechanism. Here, twenty nine analogs of HMPC were synthesized, their anti-MRSA structure-activity relationships evaluated and selectivity versus human HKC-8 cells determined. Minimum inhibitory concentrations (MIC) ranged from 0.5 to 64 μg/mL and up to 16-fold selectivity was achieved. The 4-carbodithioate function was found to be essential for activity but non-specific reactivity was ruled out as a contributor to antibacterial action. The study supports further work aimed at elucidating the molecular targets of this interesting new class of anti-MRSA agents.

Original languageEnglish (US)
Pages (from-to)3526-3528
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Issue number22
StatePublished - Dec 1 2018


  • Antibacterial
  • MgrA
  • MRSA
  • Pyrazole-4-carbodithioate
  • Staphylococcus aureus

ASJC Scopus subject areas

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


Dive into the research topics of 'Structure-activity relationships of pyrazole-4-carbodithioates as antibacterials against methicillin–resistant Staphylococcus aureus'. Together they form a unique fingerprint.

Cite this