Polypyridyl Ru(II) tamoxifen analogues: Estrogen receptor-targeted dual photodynamic and chemotherapeutic agents

IF 3.1 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2026-04-01 Epub Date: 2025-12-20 DOI:10.1016/j.jinorgbio.2025.113202

Guillermo Moreno-Alcántar , Claudia Schmidt , Darren Dennis Wragg , Riccardo Scotti , Iñigo Iribarren Aguirre , Riccardo Bonsignore , Angela Casini , Denise Lovison

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引用次数: 0

Abstract

The use of targeted chemotherapeutic agents and of locally active treatments such as photodynamic therapy (PDT), are strategies to tackle the side effects and enhance the effectiveness of anticancer treatments. In this context, the development of multifunctional drugs, which combine targeted chemotherapy and photosensitizing capabilities, has garnered increased attention. Herein, we introduce two polypyridyl ruthenium(II) compounds featuring tamoxifen-related ligands (RuTamOMe and RuTamOH) targeting the estrogen receptor α (ERα) and able to generate singlet oxygen via energy transfer. The compounds display enhanced phototoxicity, tested in different cell lines (A375 melanoma, MDA-MB-231 triple negative adenocarcinoma and MCF-7 ER+ breast cancer cells) and examined in terms of the ERα expression dependence. Computational studies were also performed, corroborating the suitability of the compounds to target ER, maintaining tamoxifen's affinity for the receptor binding site, and revealing a minimal influence of the stereochemical configuration of the compounds on their targeting capabilities. Altogether, our results highlight the potential of hybrid Ru(II) polypyridyl compounds as suitable platforms for generating targeted metallodrugs with photosensitizing capabilities.

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多吡啶Ru（II）他莫昔芬类似物：雌激素受体靶向双光动力和化疗药物

使用靶向化疗药物和局部积极治疗，如光动力治疗（PDT），是解决副作用和提高抗癌治疗有效性的策略。在这种背景下，结合靶向化疗和光敏能力的多功能药物的开发已经引起了越来越多的关注。在此，我们引入了两种多吡啶基钌（II）化合物，它们具有三苯氧胺相关配体（RuTamOMe和RuTamOH），靶向雌激素受体α (ERα)，并能够通过能量转移产生单线态氧。这些化合物在不同细胞系（A375黑色素瘤、MDA-MB-231三阴性腺癌和MCF-7 ER+乳腺癌细胞）中显示出增强的光毒性，并在ERα表达依赖性方面进行了检测。还进行了计算研究，证实了化合物靶向内质网的适用性，保持了他莫昔芬对受体结合位点的亲和力，并揭示了化合物的立体化学构型对其靶向能力的最小影响。总之，我们的研究结果突出了杂化Ru（II）聚吡啶基化合物作为产生具有光敏能力的靶向金属药物的合适平台的潜力。

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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.