Mononuclear ruthenium(ii) theranostic complexes that function as broad-spectrum antimicrobials in therapeutically resistant pathogens through interaction with DNA.
Mononuclear ruthenium(ii) theranostic complexes that function as broad-spectrum antimicrobials in therapeutically resistant pathogens through interaction with DNA.
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DOI：
10.1039/d0sc03410j
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发表时间：
2020-07-30
期刊：
影响因子：
8.4
通讯作者：
Thomas JA
中科院分区：
文献类型：
--
作者：
Smitten KL;Thick EJ;Southam HM;Bernardino de la Serna J;Foster SJ;Thomas JA
报道了六种基于四吡啶并吩嗪（tpphz）和二吡啶并吩嗪（dppz）配体的单核钌（ii）发光配合物。研究了配合物对革兰氏阴性菌（E. coli、A.鲍曼不动杆菌、铜绿假单胞菌）和革兰氏阳性菌（E. faecalis和S.金黄色葡萄球菌），包括致病性多重和泛耐药菌株。估计的最小抑菌和杀菌浓度显示，先导化合物的活性在治疗敏感菌株中与氨苄西林和苯唑西林相当，并且该活性在抗性菌株中保留。与相关的双核类似物不同，先导化合物不破坏细菌膜，但仍以葡萄糖非依赖性方式被革兰氏阳性和革兰氏阴性细菌快速摄取。通过超分辨率纳米显微镜和透射电子显微镜对复合物的直接成像显示，一旦内化，复合物的革兰氏阴性和革兰氏阳性菌株的细胞内靶标是细菌DNA。模型毒性筛选显示，即使在比细菌MIC高几个数量级的暴露浓度下，该化合物对Galleria mellonella也是无毒的。基于tpphz配体的单核钌（ii）络合物显示出对一系列AMR病原体具有宽带抗微生物治疗诊断活性。
Six luminescent, mononuclear ruthenium(ii) complexes based on the tetrapyridophenazine (tpphz) and dipyridophenazine (dppz) ligands are reported. The therapeutic activities of the complexes against Gram-negative bacteria (E. coli, A. baumannii, P. aeruginosa) and Gram-positive bacteria (E. faecalis and S. aureus) including pathogenic multi- and pan-drug resistant strains were assessed. Estimated minimum inhibitory and bactericidal concentrations show the activity of the lead compound is comparable to ampicillin and oxacillin in therapeutically sensitive strains and this activity was retained in resistant strains. Unlike related dinuclear analogues the lead compound does not damage bacterial membranes but is still rapidly taken up by both Gram-positive and Gram-negative bacteria in a glucose independent manner. Direct imaging of the complexes through super-resolution nanoscopy and transmission electron microscopy reveals that once internalized the complexes' intracellular target for both Gram-negative and Gram-positive strains is bacterial DNA. Model toxicity screens showed the compound is non-toxic to Galleria mellonella even at exposure concentrations that are orders of magnitude higher than the bacterial MIC. A mononuclear ruthenium(ii) complex based of the tpphz ligand is shown to be a broad-band antimicrobial theranostic active against a range of AMR pathogens.
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影响因子：
8.4
作者：
Gill MR;Jarman PJ;Halder S;Walker MG;Saeed HK;Thomas JA;Smythe C;Ramadan K;Vallis KA
通讯作者：
Vallis KA
影响因子：
4.6
作者：
Bolhuis, Albert;Hand, Lorna;Aldrich-Wright, Janice
通讯作者：
Aldrich-Wright, Janice
影响因子：
15
作者：
Lutterman, Daniel A.;Chouai, Abdellatif;Turro, Claudia
通讯作者：
Turro, Claudia
影响因子：
4.1
作者：
Luepke, Katherine H.;Suda, Katie J.;Mohr, John F., III
通讯作者：
Mohr, John F., III
影响因子：
64.8
作者：
DWYER, FP;GYARFAS, EC;KOCH, JH
通讯作者：
KOCH, JH