Abstract

There is clearly a need for the development of new classes of antimicrobials to fight against multidrug-resistant bacteria. Here, we designed and synthesized of three ruthenium polypyridyl complexes: [Ru(bpy)₂(BTPIP)](ClO₄)₂ (Ru(II)-1), [Ru(bpy)₂(ETPIP)](ClO₄)₂ (Ru(II)-2) and [Ru(bpy)₂(CAPIP)](ClO₄)₂ (Ru(II)-3) (N-N = bpy = 2,2′-bipyridine), their antimicrobial activities against S. aureus were assessed. The lead complexes of this set, Ru(II)-1(MIC = 0.016 mg/mL), was tested against biofilm. We also investigated whether bacteria can easily develop resistance to Ru(II)-1. The result demonstrated that S. aureus could not easily develop resistance to the ruthenium complexes. In addition, aimed to test whether ruthenium complexes treatment could increase the susceptibility of S. aureus to antibiotics, the synergism between Ru(II)-1 and common antibiotics against S. aureus were investigated using the checkerboard method. Interesting, Ru(II)-1 could increased the susceptibility of S. aureus to some aminoglycoside antibiotics(kanamycin and gentamicin). Finally, in vivo bacterial infection treatment studies were also conducted through murine skin infection model. These results confirmed ruthenium complexes have good antimicrobial activity in vitro and in vivo.

Graphic abstract

中文翻译：

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钌多吡啶基复合物对金黄色葡萄球菌和生物膜的抗菌活性。

摘要

显然，需要开发新型的抗微生物药来对抗耐多药细菌。在这里，我们设计并合成了三种钌多吡啶基配合物：[Ru（bpy）₂（BTPIP）]（ClO ₄）₂（Ru（II）-1），[Ru（bpy）₂（ETPIP）]（ClO ₄）₂（Ru（II）-2）和[Ru（bpy）₂（CAPIP）]（ClO ₄）₂（Ru（II）-3）（N - N  = bpy = 2,2'-联吡啶），它们均具有抗菌性评估了针对金黄色葡萄球菌的活性。这组的铅配合物，用生物膜测试Ru（II）-1（MIC = 0.016 mg / mL）。我们还调查了细菌是否可以轻易发展出对Ru（II）-1的抗性。结果表明，金黄色葡萄球菌不能轻易产生对钌络合物的抗性。此外，为了检验钌络合物的处理是否可以增加金黄色葡萄球菌对抗生素的敏感性，使用棋盘法研究了Ru（II）-1和常见抗生素对金黄色葡萄球菌的协同作用。有趣的是，Ru（II）-1可能会增加金黄色葡萄球菌的敏感性一些氨基糖苷类抗生素（卡那霉素和庆大霉素）。最后，还通过鼠皮肤感染模型进行了体内细菌感染治疗研究。这些结果证实了钌络合物在体外和体内均具有良好的抗菌活性。

图形摘要