Synthesis and anti-infective potency study of a Ru-based complex bearing benzonitrile against Staphylococcus aureus

Abstract

Multi drug-resistant Gram-positive pathogens have become one of the most serious problems facing humankind today. To address this challenge, there is an urgent need to develop new antimicrobial agents that are different from conventional antibiotics. Here, a Ru-based compound bearing benzonitrile, [Ru(dtb)₂(BZIL)₂](PF₆)₂ (RuBZ), was synthesized and evaluated. In vitro antibacterial studies demonstrated that RuBZ could efficiently inhibit S. aureus in vitro, showing higher potency than most existing clinical antibiotics, with a minimum inhibitory concentration value of 0.78 μg mL⁻¹. Importantly, RuBZ can effectively inhibit S. aureus from forming a biofilm and releasing hemolytic toxin. What is more, RuBZ exhibited synergistic effects when combined with four clinical antibiotics. Mechanism studies suggest that RuBZ kills bacteria by disrupting their cell membrane. In addition, RuBZ has low hemolytic toxicity and shows good anti-infective potency in two animal infection models. Above all, our study presented here indicates that the Ru-based compound containing a benzonitrile group shows good potential for use as a new anti-infective agent.