School of Pharmacy, Jiangxi Science&Technology Normal University, Nanchang 330013, China.
School of Life Science, Jiangxi Science&Technology Normal University, Nanchang 330013, China.
J Inorg Biochem. 2023 Dec;249:112385. doi: 10.1016/j.jinorgbio.2023.112385. Epub 2023 Sep 22.
Staphylococcus aureus (S. aureus), one of the Gram-positive bacteria, is easily to develop drug-resistance. Drug-resistant S. aureus infection leads to high morbidity and mortality. The complexes, namely Ru(dpa)(PSPIP) (Ru1), Ru(dpa)(TSPIP) (Ru2), and Ru(dpa)(TBPIP) (Ru3), were synthesized using 2, 2'-dipyridylamine as an auxiliary ligand and three main ligands PSPIP, TSPIP, TBPIP. In vitro studies demonstrated that the Ru1-3 exhibited excellent antibacterial activity against S. aureus while showing low hemolytic toxicity to rabbit red blood cells. Notably, Ru3 was found to disrupt the bacterial cell membrane and alter its permeability through fluorescence staining and scanning electron microscopy (SEM) analysis. Furthermore, Ru3 displayed low toxicity in G. mellonella Larvae. Ru3 exhibited good activity against S. aureus in G. mellonella Larvae infection model and mouse skin infection model.To some extent, Ru3 inhibited biofilm formation on S. aureus as well as hemolytic toxin production, thereby attenuating the development of drug resistance without cross-resistance with other antibiotics. In addition, complex Ru3 exhibited a synergistic effect when combined with antibiotics amikacin, kanamycin, tobramycin and chloramphenicol, making it a valuable antibiotics adjuvant.
金黄色葡萄球菌（S. aureus）是革兰氏阳性菌之一，容易产生耐药性。耐药性金黄色葡萄球菌感染导致高发病率和死亡率。采用 2,2'-联吡啶胺作为辅助配体和三种主要配体 PSPIP、TSPIP、TBPIP 合成了配合物Ru(dpa)(PSPIP)（Ru1）、Ru(dpa)(TSPIP)（Ru2）和Ru(dpa)(TBPIP)（Ru3）。体外研究表明，Ru1-3 对金黄色葡萄球菌具有优异的抗菌活性，同时对兔红细胞的溶血毒性较低。值得注意的是，Ru3 通过荧光染色和扫描电子显微镜（SEM）分析发现，它能破坏细菌细胞膜并改变其通透性。此外，Ru3 在 G. mellonella 幼虫中表现出低毒性。Ru3 在 G. mellonella 幼虫感染模型和小鼠皮肤感染模型中对金黄色葡萄球菌表现出良好的活性。在一定程度上，Ru3 抑制了金黄色葡萄球菌生物膜的形成和溶血毒素的产生，从而减轻了耐药性的发展，且与其他抗生素无交叉耐药性。此外，当与抗生素阿米卡星、卡那霉素、妥布霉素和氯霉素联合使用时，配合物 Ru3 表现出协同作用，使其成为一种有价值的抗生素佐剂。
