Enhanced antimicrobial and antibiofilm activities of ruthenium complexes with fluorine- and bromine-substituted ligands against staphylococcal strains

This study investigated the antimicrobial and antibiotic-potentiating activities of two novel ruthenium complexes against clinically relevant bacterial strains. The complexes cis-[RuCl2(dppb)(NN-F)] and cis-[RuCl2(dppb)(NN-Br)] exhibited activity against Staphylococcus aureus and Staphylococcus epidermidis, with minimum inhibitory concentrations (MICs) ranging from 7.8 to 62.5 µg·ml-1 and minimum bactericidal concentrations (MBCs) from 31.25 to 125 µg·ml-1. When combined with ampicillin, both complexes demonstrated synergistic effects. Time-kill assays showed bactericidal activity within the first 2 to 12 h. The complexes significantly reduced biofilm biomass, viable cell counts and metabolic activity in both biofilm formation and mature biofilms. Microscopy revealed membrane damage and increased generation of reactive oxygen species (ROS) in S. aureus biofilms. Cytotoxicity assays confirmed low toxicity toward L929 fibroblasts (≤31.2 µg·ml-1) and minimal hemolytic activity (1-13%). These findings support the potential of these ruthenium complexes as candidates for novel therapies against staphylococcal infections.