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Biological activity of manganese(i) tricarbonyl complexes on multidrug-resistant Gram-negative bacteria: From functional studies to in vivo activity in Galleria mellonella.
Metallomics ( IF 2.9 ) Pub Date : 2019-12-11 , DOI: 10.1039/c9mt00224c Paul Güntzel 1 , Christoph Nagel , Jeanette Weigelt , Jono W Betts , Calum A Pattrick , Hannah M Southam , Roberto M La Ragione , Robert K Poole , Ulrich Schatzschneider
Metallomics ( IF 2.9 ) Pub Date : 2019-12-11 , DOI: 10.1039/c9mt00224c Paul Güntzel 1 , Christoph Nagel , Jeanette Weigelt , Jono W Betts , Calum A Pattrick , Hannah M Southam , Roberto M La Ragione , Robert K Poole , Ulrich Schatzschneider
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Three new manganese(i) tricarbonyl complexes [Mn(bpqa-κ3N)(CO)3]Br, [Mn(bqpa-κ3N)(CO)3]Br, and [Mn(CO)3(tqa-κ3N)]Br as well as the previously described compound [Mn(CO)3(tpa-κ3N)]Br with bpqa = bis(2-pyridinylmethyl)(2-quinolinylmethyl)amine, bqpa = bis(2-quinolinylmethyl)(2-pyridinylmethyl)amine, tqa = tris(2-quinolinylmethyl)amine, and tpa = tris(2-pyridinylmethyl)amine were examined for their antibacterial activities on 14 different multidrug-resistant clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, in recognition of the current antimicrobial resistance (AMR) concerns with these pathogens. Minimal inhibitory concentrations (MIC) of the most potent tqa compound were in the mid-micromolar range and generally lower than that of the free ligand. Activity against both bacterial species increased with the number of quinolinylmethyl groups and lipophilicity in the order of tpa < bpqa < bqpa ≈ tqa, consistent with measured increases in release of ATP, a uniquely cytoplasmic biomolecule and induced permeability to exogenous fluorescent intercalating compounds. [Mn(CO)3(tqa-κ3N)]Br was also evaluated in the Galleria mellonella model of infection, and displayed a lack of host toxicity combined with effective bacterial clearance.
中文翻译：
三羰基锰（i）配合物对耐多药革兰氏阴性细菌的生物活性：从功能研究到梅隆商业街的体内活性。
三种新的锰（i）三羰基配合物[Mn（bpqa-κ3N）（CO）3] Br，[Mn（bqpa-κ3N）（CO）3] Br和[Mn（CO）3（tqa-κ3N）] Br以及先前描述的化合物[Mn（CO）3（tpa-κ3N）] Br，其bpqa =双（2-吡啶基甲基）（2-喹啉基甲基）胺，bqpa =双（2-喹啉基甲基）（2-吡啶基甲基）胺确认了目前的抗菌素耐药性（tqa =三（2-喹啉基甲基）胺和tpa =三（2-吡啶基甲基）胺对14种不同的鲍曼不动杆菌和铜绿假单胞菌具有多重耐药性的临床分离株的抗菌活性AMR）与这些病原体有关。最有效的tqa化合物的最小抑菌浓度（MIC）在中微摩尔范围内，通常低于游离配体的抑菌浓度。对两种细菌的活性随喹啉基甲基基团的数目和亲脂性的增加而按tpa <bpqa <bqpa≈tqa的顺序增加，这与ATP（一种独特的细胞质生物分子）释放的增加的测量值一致，并诱导了对外源荧光插层化合物的渗透性。[Mn（CO）3（tqa-κ3N）] Br也在梅勒菌感染模型中进行了评估，显示缺乏宿主毒性和有效的细菌清除能力。
更新日期：2019-12-11
中文翻译：
三羰基锰（i）配合物对耐多药革兰氏阴性细菌的生物活性：从功能研究到梅隆商业街的体内活性。
三种新的锰（i）三羰基配合物[Mn（bpqa-κ3N）（CO）3] Br，[Mn（bqpa-κ3N）（CO）3] Br和[Mn（CO）3（tqa-κ3N）] Br以及先前描述的化合物[Mn（CO）3（tpa-κ3N）] Br，其bpqa =双（2-吡啶基甲基）（2-喹啉基甲基）胺，bqpa =双（2-喹啉基甲基）（2-吡啶基甲基）胺确认了目前的抗菌素耐药性（tqa =三（2-喹啉基甲基）胺和tpa =三（2-吡啶基甲基）胺对14种不同的鲍曼不动杆菌和铜绿假单胞菌具有多重耐药性的临床分离株的抗菌活性AMR）与这些病原体有关。最有效的tqa化合物的最小抑菌浓度（MIC）在中微摩尔范围内，通常低于游离配体的抑菌浓度。对两种细菌的活性随喹啉基甲基基团的数目和亲脂性的增加而按tpa <bpqa <bqpa≈tqa的顺序增加，这与ATP（一种独特的细胞质生物分子）释放的增加的测量值一致，并诱导了对外源荧光插层化合物的渗透性。[Mn（CO）3（tqa-κ3N）] Br也在梅勒菌感染模型中进行了评估，显示缺乏宿主毒性和有效的细菌清除能力。
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