Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, 330013, China.
School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua, 418000, China.
ChemMedChem. 2023 Oct 4;18(19):e202300306. doi: 10.1002/cmdc.202300306. Epub 2023 Sep 1.
The development of antimicrobial agents with novel model of actions is a promising strategy to combat multiple resistant bacteria. Here, three ruthenium-based complexes, which acted as potential antimicrobial agents, were synthesized and characterized. Importantly, three complexes all showed strong bactericidal potency against Staphylococcus aureus. In particular, the most active one has a MIC of 6.25 μg/mL. Mechanistic studies indicated that ruthenium complex killed S. aureus by releasing ROS and damaging the integrity of bacterial cell membrane. In addition, the most active complex not only could inhibit the biofilm formation and hemolytic toxin secretion of S. aureus, but also serve as a potential antimicrobial adjuvant as well, which showed synergistic effects with eight traditional antibiotics. Finally, both G. mellonella larva infection model and mouse skin infection model all demonstrated that ruthenium complex also showed significant efficacy against S. aureus in vivo. In summary, our study suggested that ruthenium-based complexes bearing a phenyl hydroxide are promising antimicrobial agents for combating S. aureus.
新型作用模式的抗菌剂的开发是对抗多重耐药菌的一种有前途的策略。在这里，合成并表征了三种作为潜在抗菌剂的钌基配合物。重要的是，三种配合物均对金黄色葡萄球菌表现出很强的杀菌效力。特别是最活跃的一种的 MIC 为 6.25μg/mL。机制研究表明，钌配合物通过释放 ROS 和破坏细菌细胞膜完整性来杀死金黄色葡萄球菌。此外，最活跃的配合物不仅可以抑制金黄色葡萄球菌生物膜的形成和溶血毒素的分泌，而且还可以作为一种潜在的抗菌增效剂，与八种传统抗生素表现出协同作用。最后，无论是大蜡螟幼虫感染模型还是小鼠皮肤感染模型均表明，钌配合物在体内也对金黄色葡萄球菌具有显著疗效。总之，我们的研究表明，带有苯氧自由基的钌基配合物是对抗金黄色葡萄球菌的有前途的抗菌剂。
