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具有三苯胺基团的钌多吡啶配合物作为抗菌剂,具有膜破坏机制。

Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against with membrane-disruptive mechanism.

作者信息

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

机构信息

Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, China.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China.

出版信息

Front Chem. 2022 Oct 10;10:1035741. doi: 10.3389/fchem.2022.1035741. eCollection 2022.

Abstract

Due to the emergence and wide spread of methicillin-resistant , 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)PMA] (PF6) () [Ru (bpy)PMA] (PF6) () and [Ru (dmb)PMA] (PF6) () (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 was determined by single crystal X-ray diffraction. Their antibacterial activities against () were obvious and showed the best antibacterial effect with the minimum inhibitory concentration value of 4 μg ml. Therefore, further study on its biological activity showed that can effectively inhibit the formation of biofilm and destroy cell membrane. hemolysis test showed that has almost negligible cytotoxicity to mammalian red blood cells. In the toxicity test of wax moth insect model, exhibited low toxicity . These results, combined with histopathological studies, strongly suggest that was almost non-toxic. In addition, the synergistic effect of with common antibiotics such as ampicillin, chloramphenicol, tetracycline, kanamycin and gentamicin on was detected by chessboard method. Finally, results revealed that could obviously promote the wound healing of infected mice.

摘要

由于耐甲氧西林菌的出现和广泛传播,这类感染的治疗变得越来越困难。为了解决耐药性问题,迫切需要开发新的抗生素以避免出现无药可用的最严峻情况。合成了三种新型钌配合物Ru (dmob)PMA()、Ru (bpy)PMA()和Ru (dmb)PMA()(dmob = 4,4'-二甲氧基-2,2'-联吡啶,bpy = 2,2'-联吡啶,dmb = 4,4'-二甲基-2,2'-联吡啶,PMA = N-(4-(1H-咪唑并[4,5-f][1,10]菲咯啉-2-基)-4-甲基-N-(对甲苯基)苯胺),并通过1H NMR、13C NMR和高分辨质谱进行了表征。通过单晶X射线衍射确定了()的详细分子结构。它们对()的抗菌活性明显,()表现出最佳抗菌效果,最低抑菌浓度值为4 μg/ml。因此,对其生物活性的进一步研究表明,()可有效抑制生物膜形成并破坏细胞膜。()的溶血试验表明,其对哺乳动物红细胞的细胞毒性几乎可以忽略不计。在蜡螟昆虫模型的毒性试验中,()表现出低毒性。这些结果与组织病理学研究相结合,有力地表明()几乎无毒。此外,通过棋盘法检测了()与氨苄西林、氯霉素、四环素、卡那霉素和庆大霉素等常见抗生素对()的协同作用。最后,结果表明()能明显促进()感染小鼠的伤口愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af9d/9589286/cccbc8712614/fchem-10-1035741-g001.jpg

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