Water-soluble gold(III) complexes with N-donor ligands as potential immunomodulatory and antibiofilm agents

Abstract

Six gold(III) complexes with ligands of differing denticity, [HGly-Met sulfoxide][AuCl4] (1b), [Au(en)Cl2]Cl·2H2O (1c), [Au(dien)Cl]Cl2 (1d), [Au(Gly-l-His)Cl]NO3·1.25H2O (1e), [Au(l-Ala-l-His)Cl]NO3·2.5H2O (1f) and [Au(Gly-Gly-l-His)]Cl·H2O (1g), were synthesized and structurally characterized. These complexes, along with the starting compounds used for their synthesis, were tested for their immunomodulatory and antimicrobial activities. Immunomodulation was investigated by assessing their cytotoxicity towards mouse spleen lymphocytes and peritoneal macrophages. Their antimicrobial effect was tested against a panel of Gram-positive and Gram-negative bacterial strains including ATCC strains and resistant isolates. Antimicrobial potential of 1b-g was further explored by evaluating their antibiofilm activity against biofilm-forming Pseudomonas aeruginosa. All gold(III) complexes inhibited biofilm production of P. aeruginosa strains, where ethylenediamine-containing gold(III) complex 1c exhibited the strongest reduction of biofilms superseding the activity of the used antibiotic, leaving only 10% of biofilm unaffected. All investigated gold(III) complexes inhibited biofilm formation after 72 h of incubation, showing long-term effectiveness, which was visualized by microscopy during this time. The mode of antibiofilm action was evaluated by testing the effect of this complex on P. aeruginosa motility forms. Among the all investigated compounds, 1c possesses the highest both cytotoxic and antimicrobial action, making this complex a good candidate for further pharmacological evaluations.