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

Three new Ru(ii) complexes, [Ru(dtb)PPAD](PF) (), [Ru(dmob)PPAD](PF) () and [Ru(bpy)PPAD](PF) () (dtb = 4,4'-di-butyl-2,2'-bipyridine, dmob = 4,4'-dimethyl-2,2'-bipyridine, bpy = 2,2'-bipyridine and PPAD = 2-(pyridine-3-yl)-1-imidazo[4,5][1.10]phenanthracene-9,10-dione), were synthesized and characterized by H NMR and C NMR spectroscopy, HRMS and HPLC. Among them, showed excellent antimicrobial activity against Gram-positive bacteria (minimum inhibitory concentration (MIC) = 1 μg mL) and low hemolytic and cytotoxic activity. In addition, showed obviously rapid bactericidal activity, low resistance rate, bacterial biofilm destroying activity and high biosafety . Moreover, skin infection models and a mouse model of sepsis indicated that the anti-infective efficacy of 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.