Multi-target antibacterial mechanism of ruthenium polypyridine complexes with anthraquinone groups against Staphylococcus aureus .

Three new Ru(ii) complexes, [Ru(dtb) 2 PPAD](PF 6 ) 2 ( Ru-1 ), [Ru(dmob) 2 PPAD](PF 6 ) 2 ( Ru-2 ) and [Ru(bpy) 2 PPAD](PF 6 ) 2 ( Ru-3 ) (dtb = 4,4'-di -tert -butyl-2,2'-bipyridine, dmob = 4,4'-dimethyl-2,2'-bipyridine, bpy = 2,2'-bipyridine and PPAD = 2-(pyridine-3-yl)-1 H -imidazo[4,5 f ][1.10]phenanthracene-9,10-dione), were synthesized and characterized by 1 H NMR and 13 C NMR spectroscopy, HRMS and HPLC. Among them, Ru-1 showed excellent antimicrobial activity against Gram-positive bacteria Staphylococcus aureus (minimum inhibitory concentration (MIC) = 1 μg mL -1 ) and low hemolytic and cytotoxic activity. In addition, Ru-1 showed obviously rapid bactericidal activity, low resistance rate, bacterial biofilm destroying activity and high biosafety in vivo . Moreover, skin infection models and a mouse model of sepsis indicated that the anti-infective efficacy of Ru-1 was comparable to that of vancomycin. Mechanism exploration results showed that the antibacterial behavior is probably related with targeting of the bacterial cell membrane and inhibiting topoisomerase I.