Rationally designed curcumin based ruthenium(II) antimicrobials effective against drug-resistant Staphylococcus aureus

Two new curcumin containing octahedral ruthenium(II) polypyridyl complexes, viz. [Ru(NN)₂(cur)](PF₆) [NN = bpy (1), phen (2)], were designed to explore the antimicrobial activity against ESKAPE pathogens, especially with the Gram-positive drug resistant S. aureus. Solid-state structural characterization by single-crystal X-ray crystallography shows the Ru^II-center in a distorted octahedral {RuN₄O₂} geometry. The tested compounds showed significant inhibitory activity and high selectivity (MIC = 1 μg mL⁻¹, SI = 80) against a wide variety of methicillin and vancomycin-resistant S. aureus strains. Compound 1 exhibited strong anti-biofilm activity (48% reduction of biofilm) at 10× MIC compared to the other approved drugs. The murine model of Staphylococcus infection significantly reduced the mean bacterial counts when treated with complex 1 compared to vancomycin, demonstrating its antimicrobial potential in vivo.