In vitro antibacterial and time kill evaluation of mononuclear phosphanegold(I) dithiocarbamates

• Phosphanegold(I) dithiocarbamates exhibit antibacterial activity.
• All compounds are active against Gram positive bacteria.
• Alkyl dithiocarbamates are more potent than hydroxyethyl analogs.
• A variety of bacteriostatic and bactericidal activities are observed.
• Et3PAu(S2CNEt2) is the most promising candidate for further research.

Four compounds, R3PAu[S2CN(CH2CH2OH)2], R = Ph (1) and cyclohexyl (2), and Et3PAuS2CNRꞌ2, Rꞌ = Rꞌ = Et (3) and Rꞌ2 = (CH2)4 (4), have been evaluated for antibacterial activity against a panel of 24 Gram positive (8) and Gram negative (16) bacteria. Based on minimum inhibitory concentration (MIC) scores, compounds 1 and 2 were shown to be specifically potent against Gram positive bacteria whereas compounds 3 and, to a lesser extent, 4 exhibited broad range activity. All four compounds were active against methicillin resistant Staphylococcus aureus (MRSA). Time kill assays revealed the compounds to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Each compound was bactericidal against one or more bacteria with 3 being especially potent after 8 h exposure; compounds 1 and 3 were bactericidal against MRSA. Compound 3 was the most effective bactericide across the series especially toward B. subtilis, S. saprophyticus, A. hydrophila, P. vulgaris, and V. parahaemolyticus. This study demonstrates the potential of this class of compounds as antibacterial agents, either broad range or against specific bacteria.

Phosphanegold(I) dithiocarbamates display broad range anti-bacterial activity with Et3PAu(S2CNEt2) being bactericidal against both Gram positive and Gram negative bacteria.Figure optionsDownload as PowerPoint slide