Investigation of Antibacterial Activity Against Staphylococcus Aureus Of Ruthenium(II) Complexes Containing Furan-Substituted Ligands

The growing burden of antibiotic resistance worldwide calls for developing new classes of antimicrobial strategy. Recently years, the use of adjuvants that rescue antibiotics identified as a promising combination strategy for overcoming bacterial resistance. In this study, we designed and synthesized of three ruthenium complexes functionalized with furan-substituted ligands: [Ru(phen)₂(CAPIP)](ClO₄)₂  (Ru(II)-1), [Ru(dmp)₂(CAPIP)](ClO₄)₂  (Ru(II)-2) and [Ru(dmb)₂(CAPIP)](ClO₄)₂  (Ru(II)-3) (dmb=4,4′-dimethyl-2,2′-bipyridine, phen=1,10-phenanthroline, dmp=2,9-dimethyl-1,10-phenanthroline, CAPIP=(E)-2- (2-(furan-2-yl)vinyl)-1H-imidazo[4,5-f][1,10]phenanthroline). Their antimicrobial activities against S. aureus were assessed. All complexes show meaningful activity against Staphylococcus aureus with ranging MIC from 0.018-0.050 mg/mL. Importantly, the Ru(II)-2 complexes which posses minimum MIC values was further tested against biofilms and toxin secretion. The results clearly indicated Ru(II)-2 could effectively inhibit biofilms formation of S. aureus and inhibit the hemolysin toxin secretion as well. In addition, aimed to test whether ruthenium complexes have potent value as antimicrobial adjuvants, the synergism between Ru(II)-2 and common antibiotics against S. aureus were investigated using the checkerboard method. Interesting, Ru(II)-2 could selectivity increase the susceptibility of S. aureus to some aminoglycoside antibiotics. Finally,  murine skin infection model verified Ru(II)-2 were highly effective against S. aureus in vivo . Taken together, ruthenium complexes functionalized with furan-substituted ligands prepared here have good antimicrobial activity in vitro and in vivo.