Disulfiram-based disulfides as narrow-spectrum antibacterial agents. Issue 8 (1st May 2018)

• Record Type: Journal Article
• Authors: Sheppard, Jordan G.; Frazier, Keely R.; Saralkar, Pushkar; Hossain, Mohammad F.; Geldenhuys, Werner J.; Long, Timothy E.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 8(2018)
• Page Start: 1298
• Page End: 1302
• Publication Date: 2018-05-01
• Subjects: Disulfiram -- Disulfides -- Antibiotic -- Staphylococcus -- MRSA -- VISA -- VRSA; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.03.023
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.