Gold(I) N-Heterocyclic Carbene Complexes as Ferroptosis Inducing Anticancer Agents.

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2025-04-24 eCollection Date: 2025-05-08 DOI:10.1021/acsmedchemlett.5c00096

Evelyn Schlegel, Zisis Papadopoulos, Nicolás Montesdeoca, Vladislav A Voloshkin, Steven P Nolan, Stephan A Hahn, Thomas Scattolin, Johannes Karges

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引用次数: 0

Abstract

This study presents the chemical synthesis and biological evaluation of a series of gold(I)-N-heterocyclic carbene complexes as potential anticancer agents. The compounds demonstrated broad activity against various cancer cell lines, exhibiting cytotoxicity in the low micromolar range. Mechanistic investigations revealed that these complexes preferentially accumulate in the mitochondria of cancer cells, where they induce the generation of reactive oxygen species and lipid peroxides, ultimately triggering ferroptosis. Further studies in multicellular tumor spheroids confirmed the compounds' ability to penetrate three-dimensional cellular structures and effectively eradicate them at low micromolar concentrations. This work represents the first known example of a gold(I)-N-heterocyclic carbene complex inducing ferroptosis, expanding the therapeutic potential of gold(I)-based metallodrugs.

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金(I) n -杂环卡宾配合物作为诱导铁下垂的抗癌剂。

本文介绍了一系列金(I)- n杂环碳配合物的化学合成和生物学评价。化合物对多种癌细胞具有广泛的活性，在低微摩尔范围内表现出细胞毒性。机制研究表明，这些复合物优先积聚在癌细胞的线粒体中，在那里它们诱导活性氧和脂质过氧化物的产生，最终引发铁下垂。对多细胞肿瘤球体的进一步研究证实了该化合物能够穿透三维细胞结构，并在低微摩尔浓度下有效地根除它们。这项工作代表了已知的第一个金(I)- n -杂环卡宾复合物诱导铁下垂的例子，扩大了金(I)基金属药物的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.