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N,N'-亚油烯基双咪唑𬭩金(I)盐是一种控制与角膜炎相关的眼部感染的有效候选物。

N, N'-Olefin functionalized bis-imidazolium gold(I) salt is an efficient candidate to control keratitis-associated eye infection.

机构信息

School of Applied Sciences, Haldia Institute of Technology, Haldia, West Bengal, India.

出版信息

PLoS One. 2013;8(3):e58346. doi: 10.1371/journal.pone.0058346. Epub 2013 Mar 15.

Abstract

Keratitis treatment has become more complicated due to the emergence of bacterial or fungal pathogens with enhanced antibiotic resistance. The pharmaceutical applications of N-heterocyclic carbene complexes have received remarkable attention due to their antimicrobial properties. In this paper, the new precursor, 3,3'-(p-phenylenedimethylene) bis{1-(2- methyl-allyl)imidazolium} bromide (1a) and its analogous PF6 salt (1b) were synthesized. Furthermore, silver(I) and gold(I) -N-heterocyclic carbene (NHC) complexes [Ag2LBr2/Au2LBr2; 2a/3a], [(Ag2L2)(PF6)2/(Au2L2)(PF6)2; 2b/3b] were developed from their corresponding ligands. All compounds were screened for their antimicrobial activities against multiple keratitis-associated human eye pathogens, including bacteria and fungi. Complexes 2a and 3a showed highest activity, and the effectiveness of 3a was also studied, focusing eradication of pathogen biofilm. Furthermore, the structures of 1a, 2a and 3b were determined using single crystal X-ray analysis, 2b and 3a were optimized theoretically. The mechanism of action of 3a was evaluated by scanning electron microscopy and docking experiments, suggesting that its target is the cell membrane. In summary, 3a may be helpful in developing antimicrobial therapies in patients suffering from keratitis-associated eye infections caused by multidrug-resistant pathogens.

摘要

由于具有增强抗生素耐药性的细菌或真菌病原体的出现,角膜炎的治疗变得更加复杂。由于具有抗菌特性,N-杂环卡宾配合物的药物应用受到了极大的关注。在本文中,合成了新的前体 3,3'-(对苯二亚甲基)双{1-(2-甲基烯丙基)咪唑啉}溴化物(1a)及其类似的 PF6 盐(1b)。此外,还从其相应的配体开发了银(I)和金(I)-N-杂环卡宾(NHC)配合物[Ag2LBr2/Au2LBr2;2a/3a],[(Ag2L2)(PF6)2/(Au2L2)(PF6)2;2b/3b]。所有化合物都针对多种与角膜炎相关的人眼病原体(包括细菌和真菌)进行了抗微生物活性筛选。配合物 2a 和 3a 表现出最高的活性,还研究了 3a 的有效性,重点是消除病原体生物膜。此外,使用单晶 X 射线分析确定了 1a、2a 和 3b 的结构,理论上优化了 2b 和 3a。通过扫描电子显微镜和对接实验评估了 3a 的作用机制,表明其靶标是细胞膜。总之,3a 可能有助于开发针对由多药耐药病原体引起的角膜炎相关眼部感染的抗菌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a811/3598898/8d91f59a493f/pone.0058346.g001.jpg

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