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吡嗪功能化的 Ag(I) 和 Au(I)-NHC 配合物是有潜力的抗菌剂。

Pyrazine functionalized Ag(I) and Au(I)-NHC complexes are potential antibacterial agents.

机构信息

School of Applied Sciences, Haldia Institute of Technology, Haldia -721657, WB, India.

出版信息

Curr Med Chem. 2012;19(24):4184-93. doi: 10.2174/092986712802430090.

Abstract

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Bacteria can develop ways to render traditional antibiotics ineffective, raising a crucial need to find new antimicrobials with novel mode of action. We demonstrate here a novel class of pyrazine functionalized Ag(I) and Au(I)-NHC complexes as antibacterial agents against human pathogens that are resistant to several antibiotics. Complete synthetic and structural studies of Au(I) and Ag(I) complexes of 2-(1-methylimidazolium) pyrimidinechloride (L-1), 2,6-bis(1-methylimidazol)pyrazinechloride (L-2) and 2,6-bis(1-methyl imidazol) pyrazinehexa-fluorophosphate (L-3) are reported herein. Chloro[2,6-bis(1-methyl imidazol)pyrazine]gold(I), 2b and chloro [2,6-bis(1-methyl imidazol)pyrazine]silver(I), 2a complexes are found to have more potent antimicrobial activity than other synthesized compounds and several conventionally used antibiotics. Complexes 2b and 2a also inhibit the biofilm formation by Gram-positive bacteria, Streptococcus mutans and Gram-negative bacteria, Escherichia coli, causing drastic damage to the bacterial cell wall and increasing membrane permeability. Complexes 2b and 2a strongly binds to both Lys and Dap-Type peptidoglycan layers, which may be the reason for damage to the bacterial cell wall. Theoretical studies of all the complexes reveal that 2b and 2a are more reactive than other complexes, and this may be the cause of differences in antibacterial activity. These findings will pave the way towards developing a new class of antibiotics against different groups of conventional antibiotic-resistant bacteria.

摘要

抗微生物耐药性是全世界日益严重的问题,已经达到严重程度。细菌可以发展出使传统抗生素无效的方法,因此迫切需要找到具有新型作用模式的新抗菌药物。我们在这里展示了一类新的吡嗪功能化的 Ag(I)和 Au(I)-NHC 配合物,它们是针对对多种抗生素具有耐药性的人类病原体的抗菌剂。本文报道了 2-(1-甲基咪唑)嘧啶氯化物 (L-1)、2,6-双(1-甲基咪唑)吡嗪氯化物 (L-2)和 2,6-双(1-甲基咪唑)吡嗪六氟磷酸盐 (L-3)的 Au(I)和 Ag(I)配合物的完整合成和结构研究。发现[2,6-双(1-甲基咪唑)吡嗪]氯金 (I),2b 和 [2,6-双(1-甲基咪唑)吡嗪]氯银 (I),2a 配合物具有比其他合成化合物和几种常规使用的抗生素更强的抗菌活性。配合物 2b 和 2a 还抑制革兰氏阳性菌变形链球菌和革兰氏阴性菌大肠杆菌的生物膜形成,导致对细菌细胞壁的严重破坏并增加膜通透性。配合物 2b 和 2a 强烈结合到 Lys 和 Dap-Type 肽聚糖层,这可能是破坏细菌细胞壁的原因。所有配合物的理论研究表明,2b 和 2a 比其他配合物更具反应性,这可能是抗菌活性差异的原因。这些发现将为开发针对不同常规抗生素耐药细菌群的新型抗生素铺平道路。

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