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首页> 外文期刊>Chemistry: A European journal >Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of Mammalian and Bacterial Thioredoxin Reductases, and Gram-Positive Directed Antibacterial Effects
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Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of Mammalian and Bacterial Thioredoxin Reductases, and Gram-Positive Directed Antibacterial Effects

机译：黄金（i）NHC复合物：抗增殖活性，细胞吸收，哺乳动物抑制和细菌硫氧嗪还原酶，以及革兰氏阳性定向抗菌作用

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摘要

Gold complexes with N-heterocyclic carbene (NHC) ligands represent a promising class of metallodrugs for the treatment of cancer or infectious diseases. In this report, the synthesis and the biological evaluation of halogen- containing NHC-Au~I-Cl complexes are described. The complexes 1 and 5a-5 f displayed good cytotoxic activity against tumor cells, and cellular uptake studies suggested that an intact Au-NHC fragment is essential for the accumulation of high amounts of both the metal and the NHC ligand. However, the bioavailability was negatively affected by serum components of the cell culture media and was influenced by likely transformations of the complex. One example (5d) efficiently induced apoptosis in vincristine- and daunorubicin-resistant P-glycoprotein overexpressing Nalm-6 leukemia cells. Cellular uptake studies with this compound showed that both the wild-type and resistant Nalm-6 cells accumulated comparable amounts of gold, indicating that the gold drug was not excreted by P-glycoprotein or other efflux transporters. The effective inhibition of mammalian and bacterial thioredoxin reductases (TrxR) was confirmed for all of the gold complexes. Antibacterial screening of the gold complexes showed a particularly high activity against Gram-positive strains, reflecting their high dependence on an intact Trx/TrxR system. This result is of particular interest as the inhibition of bacterial TrxR represents a relatively little explored mechanism of new anti-infectives.
机译：具有N-杂环卡宾（NHC）配体的金色络合物代表了一种用于治疗癌症或传染病的美金药等阶级。在本报告中，描述了含卤素NHC-Au〜I-Cl复合物的合成和生物学评价。复合物1和5A-5F针对肿瘤细胞显示出良好的细胞毒性活性，并且细胞摄取性研究表明，完整的Au-NHC片段对于大量金属和NHC配体的积累是必不可少的。然而，生物利用度受细胞培养基的血清组分受到负面影响，并且受到复合物的可能转化的影响。一个例子（5D）有效地诱导血压和Daunorubicin抗性P-糖蛋白过表达的纳米-6白血病细胞中的细胞凋亡。具有该化合物的细胞摄取研究表明，野生型和抗性NALM-6细胞累积了相当的金量，表明金药物未被p-糖蛋白或其他流出转运蛋白排出。对所有金络合物确认了对哺乳动物和细菌硫氧化辛还原酶（TRXR）的有效抑制。金络合物的抗菌筛选表现出对革兰氏阳性菌株的特别高的活性，反映了它们对完整的TRX / TRXR系统的高依赖性。这种结果特别感兴趣，因为对细菌TRXR的抑制代表了新的抗感染性的相对较少的探索机制。

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  • 来源
    《Chemistry: A European journal》 |2017年第8期|共12页
  • 作者

    Claudia Schmidt; Bianka Karge; Rainer Misgeld; Aram Prokop; Raimo Franke; Mark Br?nstrup; Ingo Ott;

  • 作者单位

    Institute of Medicinal and Pharmaceutical Chemistry Technische Universit?t Braunschweig Beethovenstrasse 55 38106 Braunschweig (Germany);

    Department of Chemical Biology Helmholtz Centre for Infection Research GmbH Inhoffenstrasse 7 38124 Braunschweig (Germany);

    Department of Paedriatric Oncology Children's Hospital Cologne Amsterdamer Strasse 59 50735 Cologne (Germany);

    Department of Paedriatric Oncology Children's Hospital Cologne Amsterdamer Strasse 59 50735 Cologne (Germany);

    Department of Chemical Biology Helmholtz Centre for Infection Research GmbH Inhoffenstrasse 7 38124 Braunschweig (Germany);

    Department of Chemical Biology Helmholtz Centre for Infection Research GmbH Inhoffenstrasse 7 38124 Braunschweig (Germany);

    Institute of Medicinal and Pharmaceutical Chemistry Technische Universit?t Braunschweig Beethovenstrasse 55 38106 Braunschweig (Germany);

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 应用化学;
  • 关键词

    antibiotics; cancer; atomic absorption spectroscopy; gold complexes; N-heterocyclic carbenes; thioredoxin reductase;

    机译：抗生素;癌症;原子吸收光谱;金络合物;正杂环碳;硫氧嘧啶还原酶;

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