Indium(III) 8-hydroxyquinolinates: Activity and selectivity towards multi-drug resistant strains of Klebsiella pneumoniae

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2025-08-08 DOI:10.1016/j.jinorgbio.2025.113024

Charles R.M. Soukup , Rebekah N. Duffin , Laurence Meagher , Philip C. Andrews

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Abstract

A series of dimethyl indium(III) 8-hydroxyquinolinates; [InMe₂(Q")] (1), [InMe₂(Q'Cl)] (2), [InMe₂(QCl₂)] (3), [InMe₂(QBr₂)] (4), [InMe₂(QI₂)] (5), [InMe₂(QICl)] (6), and a series of indium(III) tris(8-hydroxyquinolinates); [In(Q")₃]•H₂O (7), [In(QCl₂)₃] (8), [In(QBr₂)₃] (9), [In(QI₂)₃] (10), and [In(QICl)₃] (11), (where Q"-H = C₉H₇NO; Q'Cl-H = C₉H₆NOCl, QCl₂-H = C₉H₅NOCl₂; QBr₂-H = C₉H₅NOBr₂; QI₂-H = C₉H₅NOI₂; and QICl-H = C₉H₅NOICl) were synthesised, characterised, and evaluated for their antibacterial activity against Gram-positive bacteria (vancomycin-resistant E. faecalis, S. aureus, methicillin-resistant S. aureus), Gram-negative bacteria (K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli) and mammalian cell inhibition of L929 fibroblasts. Single crystal X-ray diffraction data of 2–4 indicates the dimethylindium complexes are dimeric in the solid-state through ‘In₂O₂’ bridging. Complexes 1–6 exhibit significant activity and selectivity against three multi-drug resistant strains of K. pneumoniae, with MIC (minimum inhibitory concentration) values as low as 49 nM and selectivity indices as high as 159 against carbapenem-resistant strain RH201207. The antibacterial activity and selectivity against K. pneumoniae is generally enhanced upon complexation of the 8-hydroxyquinolinate ligands to indium(III).

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铟（III） 8-羟基喹啉酸盐：对肺炎克雷伯菌多重耐药菌株的活性和选择性

一系列二甲基铟（III） 8-羟基喹啉酸酯[InMe2（Q′）](1),[InMe2(Q′cl)] (2), [InMe2(QCl2)] (3), [InMe2(QBr2)] (4), [InMe2(QI2)] (5), [InMe2(QICl)](6)，以及一系列铟（III）三羟基喹啉酸盐；((Q ") 3)水(7),((QCl2) 3) (8) ((QBr2) 3) (9) ((QI2) 3)(10)和((QICl) 3) (11), (Q - h = C9H7NO; Q 'Cl-H = C9H6NOCl QCl2-H = C9H5NOCl2; QBr2-H = C9H5NOBr2; QI2-H = C9H5NOI2;和QICl-H = C9H5NOICl)对革兰氏阳性菌（耐万古霉素粪大肠杆菌、金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌）、革兰氏阴性菌（肺炎克雷伯菌、鲍曼杆菌、铜绿假单胞菌和大肠杆菌）和哺乳动物细胞L929成纤维细胞的抑菌活性进行了合成、表征和评价。2-4的单晶x射线衍射数据表明，二甲基铟配合物通过“In2O2”桥接在固态中是二聚体。配合物1-6对3株多重耐药肺炎凯布菌具有显著的活性和选择性，对碳青霉烯类耐药菌株RH201207的MIC（最小抑制浓度）值低至49 nM，选择性指数高达159。8-羟基喹啉酸配体与铟（III）络合后，对肺炎克雷伯菌的抗菌活性和选择性普遍增强。

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来源期刊

Journal of Inorganic Biochemistry 生物-生化与分子生物学

CiteScore

7.00

自引率

10.30%

发文量

336

审稿时长

41 days

期刊介绍： The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.