Disulfiram-based disulfides as narrow-spectrum antibacterial agents

Bioorg Med Chem Lett. 2018 May 1;28(8):1298-1302. doi: 10.1016/j.bmcl.2018.03.023. Epub 2018 Mar 10.

Abstract

Sixteen disulfides derived from disulfiram (Antabuse™) were evaluated as antibacterial agents. Derivatives with hydrocarbon chains of seven and eight carbons in length exhibited antibacterial activity against Gram-positive Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Listeria spp. A comparison of the cytotoxicity and microsomal stability with disulfiram further revealed that the eight carbon chain analog was of lower toxicity to human hepatocytes and has a longer metabolic half-life. In the final analysis, this investigation concluded that the S-octylthio derivative is a more effective growth inhibitor of Gram-positive bacteria than disulfiram and exhibits more favorable cytotoxic and metabolic parameters over disulfiram.

Keywords: Antibiotic; Disulfides; Disulfiram; MRSA; Staphylococcus; VISA; VRSA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Ciprofloxacin / pharmacology
  • Disulfiram / analogs & derivatives*
  • Disulfiram / chemical synthesis
  • Disulfiram / pharmacology*
  • Disulfiram / toxicity
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Half-Life
  • Hep G2 Cells
  • Humans
  • Microbial Sensitivity Tests
  • Microsomes, Liver / drug effects
  • Molecular Structure
  • Rats
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Ciprofloxacin
  • Vancomycin
  • Disulfiram