Synthesis and biological evaluation of ruthenium complexes bearing the 1,2,4-triazole group as potential membrane-targeting antibacterial agents towards Staphylococcus aureus

Abstract

Bacterial infection is one of the most serious public health problems, being harmful to human health and expensive. Nowadays, the misuse and overuse of antibiotics have led to the emergence of drug resistance. Therefore, it is an urgent need to develop new antimicrobial agents to address the current situation. In this study, four 1,2,4-triazole ruthenium polypyridine complexes [Ru(bpy)₂(TPIP)](PF₆)₂ (Ru1), [Ru(dmb)₂(TPIP)](PF₆)₂ (Ru2), [Ru(dtb)₂(TPIP)](PF₆)₂ (Ru3) and [Ru(dmob)₂(TPIP)](PF₆)₂ (Ru4) (bpy = 2,2′-bipyridine, dmb = 4,4′-dimethyl-2,2′-bipyridine, dtb = 4,4′-di-tert-butyl-2,2′-bipyridine, dmob = 4,4′-dimethoxy-2,2′-bipyridine and TPIP = 2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and evaluated for antibacterial activity. Results showed that the minimum inhibitory concentration (MIC) value of Ru3 against Staphylococcus aureus (S. aureus) was only 0.78 μg mL⁻¹, showing the best antimicrobial activity in vitro. Besides, Ru3 showed low hemolytic activity and good biocompatibility. Due to its ability to damage the cell membrane of Staphylococcus bacteria, Ru3 was able to kill bacteria in a short time. Importantly, by inhibiting bacterial toxins and the formation of biofilm, Ru3 was not susceptible to the development of drug resistance. Moreover, Ru3 revealed excellent therapeutic effects in vivo and showed no irritation to the skin of mice. In conclusion, the four obtained 1,2,4-triazole ruthenium polypyridine complexes show strong antibacterial activity and satisfactory biocompatibility with excellent potential for antibacterial treatment, and provide a new solution for the current antibacterial crisis.