AUTHOR=Jiang Li , Ma Yuanyuan , Xiong Yanshi , Tan Yanhui , Duan Xuemin , Liao Xiangwen , Wang Jintao 

TITLE=Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.1035741

DOI=10.3389/fchem.2022.1035741

ISSN=2296-2646

ABSTRACT=<p>Due to the emergence and wide spread of methicillin-resistant <italic>Staphylococcus aureus</italic>, the treatment of this kind of infection becomes more and more difficult. To solve the problem of drug resistance, it is urgent to develop new antibiotics to avoid the most serious situation of no drug available. Three new Ru complexes [Ru (dmob)<sub>2</sub>PMA] (PF6)<sub>2</sub> (<bold>Ru-1</bold>) [Ru (bpy)<sub>2</sub>PMA] (PF6)<sub>2</sub> (<bold>Ru-2</bold>) and [Ru (dmb)<sub>2</sub>PMA] (PF6)<sub>2</sub> (<bold>Ru-3</bold>) (dmob = 4,4′-dimethoxy-2,2′-bipyridine, bpy = 2,2′-bipyridine, dmb = 4,4′-dimethyl-2,2′-bipyridine and PMA = N-(4-(1H-imidazo [4,5-f] [1,10] phenanthrolin-2-yl) -4-methyl-N-(p-tolyl) aniline) were synthesized and characterized by 1H NMR, 13C NMR and HRMS. The detailed molecular structure of <bold>Ru-3</bold> was determined by single crystal X-ray diffraction. Their antibacterial activities against <italic>Staphylococcus aureus</italic> (<italic>Staphylococcus aureus</italic>) were obvious and <bold>Ru-3</bold> showed the best antibacterial effect with the minimum inhibitory concentration value of 4 μg ml<sup>−1</sup>. Therefore, further study on its biological activity showed that <bold>Ru-3</bold> can effectively inhibit the formation of biofilm and destroy cell membrane. <italic>In vitro</italic> hemolysis test showed that <bold>Ru-3</bold> has almost negligible cytotoxicity to mammalian red blood cells. In the toxicity test of wax moth insect model, <bold>Ru-3</bold> exhibited low toxicity <italic>in vivo</italic>. These results, combined with histopathological studies, strongly suggest that <bold>Ru-3</bold> was almost non-toxic. In addition, the synergistic effect of <bold>Ru-3</bold> with common antibiotics such as ampicillin, chloramphenicol, tetracycline, kanamycin and gentamicin on <italic>Staphylococcus aureus</italic> was detected by chessboard method. Finally, <italic>in vivo</italic> results revealed that <bold>Ru-3</bold> could obviously promote the wound healing of <italic>Staphylococcus aureus</italic> infected mice.</p>