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钌、锇、铱和铑半夹心型配合物与双齿单糖配体靶向多重耐药革兰氏阳性菌

Targeting Multiresistant Gram-Positive Bacteria by Ruthenium, Osmium, Iridium and Rhodium Half-Sandwich Type Complexes With Bidentate Monosaccharide Ligands.

作者信息

Balázs Bence, Tóth Zoltán, Kacsir István, Sipos Adrienn, Buglyó Péter, Somsák László, Bokor Éva, Kardos Gábor, Bai Péter

机构信息

Department of Metagenomics, University of Debrecen, Debrecen, Hungary.

Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary.

出版信息

Front Chem. 2022 Apr 12;10:868234. doi: 10.3389/fchem.2022.868234. eCollection 2022.

Abstract

Bacterial resistance to antibiotics is an ever-growing problem in heathcare. We have previously identified a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich type complexes with bidentate monosaccharide ligands possessing cytostatic properties against carcinoma, lymphoma and sarcoma cells with low micromolar or submicromolar IC values. Importantly, these complexes were not active on primary, non-transformed cells. These complexes have now been assessed as to their antimicrobial properties and found to be potent inhibitors of the growth of reference strains of and (Gram-positive species), though the compounds proved inactive on reference strains of and (Gram-negative species and fungi). Furthermore, clinical isolates of and sp. (both multiresistant and susceptible strains) were also susceptible to the organometallic complexes in this study with similar MIC values as the reference strains. Taken together, we identified a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich type antineoplastic organometallic complexes which also have antimicrobial activity among Gram-positive bacteria. These compounds represent a novel class of antimicrobial agents that are not detoxified by multiresistant bacteria suggesting a potential to be used to combat multiresistant infections.

摘要

细菌对抗生素的耐药性是医疗保健领域一个日益严重的问题。我们之前已经鉴定出一组锇(II)、钌(II)、铱(III)和铑(III)的半夹心型配合物,它们带有双齿单糖配体,对癌细胞、淋巴瘤细胞和肉瘤细胞具有细胞抑制特性,其半数抑制浓度(IC)值处于低微摩尔或亚微摩尔水平。重要的是,这些配合物对原代未转化细胞没有活性。现在已经对这些配合物的抗菌特性进行了评估,发现它们是金黄色葡萄球菌和枯草芽孢杆菌(革兰氏阳性菌)参考菌株生长的有效抑制剂,不过这些化合物对大肠杆菌和白色念珠菌(革兰氏阴性菌和真菌)的参考菌株没有活性。此外,在本研究中,肺炎克雷伯菌和鲍曼不动杆菌的临床分离株(包括多重耐药菌株和敏感菌株)也对这些有机金属配合物敏感,其最低抑菌浓度(MIC)值与参考菌株相似。综上所述,我们鉴定出了一组锇(II)、钌(II)、铱(III)和铑(III)的半夹心型抗肿瘤有机金属配合物,它们在革兰氏阳性菌中也具有抗菌活性。这些化合物代表了一类新型抗菌剂,多重耐药细菌无法使其解毒,这表明它们具有用于对抗多重耐药感染的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2131/9039051/93fe11f2122f/fchem-10-868234-g001.jpg

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