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Published on: December 4, 2016
Disulfiram-based disulfides as narrow-spectrum antibacterial agents
Jordan G Sheppard1, Keely R Frazier1, Pushkar Saralkar2
1Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
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.
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