Synthesis and biological evaluation of ruthenium complexes containing phenylseleny against Gram-positive bacterial infection by damage membrane integrity and avoid drug-resistance

Compounds modified with selenium atom as potential antibacterial agents have been exploited to combat the nondrug-resistant bacterial infection. In this study, we designed and synthesized four ruthenium complexes retouching of selenium-ether. Fortunately, those four ruthenium complexes shown excellent antibacterial bioactive (MIC: 1.56-6.25 mu g/mL) against Staphylococcus aureus (S. aureus), and the most active complex Ru(II)-4 could kill S. aureus by targeting the membrane integrity and avoid the bacteria to evolve drug resistance. Moreover, Ru(II)-4 was found to significantly inhibit the formation of biofilms and biofilm eradicate capacity. In toxicity experiments, Ru(II)-4 exhibited poor hemolysis and low mammalian toxicity. To illustrate the anti-bacterial mechanism: we conducted scanning electron microscope (SEM), fluorescent staining, membrane rupture and DNA leakage assays. Those results demonstrated that Ru(II)-4 could destroy the integrity of bacterial cell membrane. Furthermore, both G. mellonella wax worms infection model and mouse skin infection model were established to evaluate the antibacterial activity of Ru(II)-4 in vivo, the results indicated that Ru(II)-4 was a potential candidate for combating S. aureus infections, and almost non-toxic to mouse tissue. Thus, all the results indicated that introducing selenium-atom into ruthenium compounds were a promising strategy for developing interesting antibacterial agents.

Automated summary

In this study, four ruthenium complexes modified with selenium-ether were synthesized and showed excellent antibacterial activity against Staphylococcus aureus (S. aureus). The most active complex, Ru(II)-4, efficiently targeted the bacterial cell membrane, preventing drug resistance and inhibiting biofilm formation. In toxicity experiments, Ru(II)-4 exhibited low mammalian toxicity. In vivo tests using both G. mellonella wax worms and mouse skin infection models confirmed the potential of Ru(II)-4 as an effective antibacterial agent against S. aureus infections, with minimal toxicity to mouse tissue. These findings highlight the promising strategy of introducing selenium-atom into ruthenium compounds for developing interesting antibacterial agents.