In the search for new gold metalloantibiotics: In vitro evaluation of Au(III) (C^S)-cyclometallated complexes

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2024-09-10 DOI:10.1016/j.jinorgbio.2024.112735

Paula Pérez-Ramos , Yaiza Gabasa , Enmanuel Cornielle , Humberto Rodríguez-Solla , Sara M. Soto , Raquel G. Soengas

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引用次数: 0

Abstract

A series of (C^S)-cyclometallated Au(III) cationic complexes of general formula [Au(dppta)(dtc)]⁺, [Au(dppta)(azmtd)]⁺ and [Au(dppta)(azc)Cl]⁺ (dppta = N,N-diisopropyl-P,P-diphenylphosphinothioic amide-κ²C,S; dtc = dithiocarbamate-κ²S,S′; azc = azolium-2-dithiocarboxylate-κ¹S; azmdt = azol(in)ium-2-(methoxy)methanedithiol-κ²S,S′) were synthetized and tested against a panel of bacterial strains belonging to different Gram-positive and Gram-negative species of the ESKAPE group of pathogens. Among the tested compounds, complex 4c had the higher Therapeutic Index (TI) against multidrug resistant strains of S. aureus, S. epidermidis and A. baumannii, showing a more favourable cytotoxicity profile than the reference gold metalloantibiotic Auranofin.

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寻找新的金金属抗生素：Au(III)(C^S)环金属化配合物的体外评估

一系列通式为[Au(dppta)(dtc)]+、[Au(dppta)(azmtd)]+和[Au(dppta)(azc)Cl]+的(C^S)-环金属化 Au(III)阳离子配合物（dppta = N,N-二异丙基-P,P-二苯基硫代磷酸酰胺-κ2C,S；dtc = 二硫代氨基甲酸酯-κ2S,S′；azc=偶氮鎓-2-二硫代羧酸盐-κ1S；azmdt=偶氮(内)鎓-2-(甲氧基)甲二硫醇-κ2S,S′）合成，并针对 ESKAPE 类病原体中不同革兰氏阳性和革兰氏阴性细菌菌株进行了测试。在测试的化合物中，复合物 4c 对金黄色葡萄球菌、表皮葡萄球菌和鲍曼尼氏菌等多重耐药菌株的治疗指数（TI）较高，显示出比参考金金属抗生素 Auranofin 更有利的细胞毒性特征。由 Elsevier B.V. 托管。保留所有权利。

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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.