含三苯胺衍生物取代钌配合物的合成及其抗菌活性研究  

Synthesis and antibacterial activities of ruthenium complexes with triphenylamine derivative ligands

作　　者：曾威 姜雯雯[1] 马丹丹[1] 陈晓燕[1] 荣小娟 马兆霞 Zeng Wei;Jiang Wenwen;Ma Dandan;Chen Xiaoyan;Rong Xiaojuan;Ma Zhaoxia(School of Medicine,Jiangxi University of Technology,Nanchang 330011)

机构地区：[1]江西科技学院医学院,南昌330011

出　　处：《中国抗生素杂志》2023年第10期1141-1150,共10页Chinese Journal of Antibiotics

基　　金：江西省教育厅科技项目(No.GJJ202015,No.GJJ202016);江西省卫健委科技计划项目(No.202211352);江西科技学院自然科学基金项目(No.ZR2002)。

摘　　要：目的 以三苯胺取代邻菲啰啉衍生物为主配体,合成了两种新型的抗菌钌配合物[Ru(phen)2PMA](PF6)2(Ru-1)和[Ru(dmphen)2PMA](PF6)2(Ru-2)。方法 通过1HNMR、13CNMR和HRMS对两个化合物的结构进行了表征,并通过最低抑菌浓度,生长曲线,时间杀伤曲线,生物膜形成实验,耐药测试,溶血毒素分泌实验以及棋盘联用实验研究了化合物的抗菌活性;通过DAPI/PI染色实验以及蛋白质泄露实验研究了化合物的抗菌机制;最后通过大蜡螟幼虫研究了化合物的毒性。结果 两个化合物在体外对金黄色葡萄球菌均具有显著抗菌活性(MIC=0.0078~0.0156 mg/mL),0.031 mg/mL的Ru-2能在10 min杀灭超过99.0%的细菌。在亚抑菌浓度下,Ru-2不仅能有效抑制细菌生物膜的形成和溶血毒素的分泌,还能显著提升8种临床常用抗生素对金黄色葡萄球菌的敏感性(FICI<0.5)。抑菌机制研究结果表明,化合物Ru-2能破坏细菌细胞壁的完整性。此外,毒性研究也表明Ru-2具有良好的生物相容性;结论 具有膜破坏机制的金属钌配合物在抗金黄色葡萄球菌感染方面具有潜在的应用前景。Objective Two antibacterial ruthenium complexes bearing triphenylamine derivative:[Ru(phen)2PMA](PF6)2(Ru-1)and[Ru(dmphen)2PMA](PF6)2(Ru-2)were synthesized.Methods Two complexes were characterized by 1H NMR,13C NMR,and HRMS.The antibacterial activity of these two compounds in vitro were studied via the minimum inhibitory concentration(MIC),the bacterial growth curve,the time killing assay,the biofilm formation assay,the drug resistance develop assay,and the hemolytic toxin and checkboard assay.Results Two compounds have strong antibacterial activity against Staphylococcus aureus(S.aureus)in vitro(0.0078~0.0156 mg/mL).Complex Ru-2 could kill 99.0%bacteria in 10 minutes.In addition,the formation of biofilm and the secretion of hemolytic toxin of bacteria were significantly inhibited by Ru-2 at the subinhibitory concentration.More importantly,Ru-2 showed synergistic effects with eight traditional antibiotics.Further studies on its antibacterial mechanism showed that Ru-2 destroyed bacterial cell membrane.At last,toxicity study also indicated that Ru-2 has good biocompatibility.Conclusion Ruthenium complexes with membrane-disruptive activity is a potential antibacterial strategy to combating S.aureus.

关 键 词：钌配合物 三苯胺衍生物 抗菌机制 抗菌活性 

分 类 号：R916[医药卫生—药学]