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

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 8h 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.