Exploring the Anticancer Properties of 4-Phenylthiazole-Based Ru(II) and Os(II) Metallacycles Featuring 1-Methylimidazole as N-Donor Functionality.

IF 4.1 3区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioinorganic Chemistry and Applications Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI:10.1155/bca/6352081

Paul Getreuer, Theresa Mendrina, Steven van Terwingen, Laura Marretta, Orsolya Dömötör, Dominik Wenisch, Michaela Hejl, Petra Heffeter, Walter Berger, Michael A Jakupec, Alessio Terenzi, Bernhard K Keppler, Wolfgang Kandioller

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引用次数: 0

Abstract

Ten organometallic complexes of the general formula [M(p-cymene)thi_CΛNMeIm]NO₃ (M = Ru, Os; MeIm = 1-methylimidazole, thi = 4-phenylthiazole) differing in their substituents on the 4-phenylthiazole scaffold were prepared and characterized by standard analytical methods. The antiproliferative activity of the compounds was investigated in human lung adenocarcinoma (A549), colon adenocarcinoma (SW480), and human ovarian teratocarcinoma (CH1/PA-1) cell lines. IC₅₀ values were in the low micromolar range with two exceptions. Additionally, the cytotoxicity of selected compounds was determined in the HCT116 colon carcinoma cell line in both 2D (monolayer) and 3D (multicellular spheroid) cultures. For selected compounds, the capacity of ROS induction was investigated in SW480 cells. Cellular accumulation experiments, as well as studies regarding stability and reactivity in aqueous solution, were performed, providing conclusive explanations for the observed differences in cytotoxicity. Furthermore, amino acid and DNA interaction studies were performed to elucidate aspects of the mechanism of action. The obtained insight into the antiproliferative activity in multicellular spheroids compelled us to perform in vivo studies, revealing the unexpected therapeutic efficacy of an in vitro inactive complex.

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以1-甲基咪唑为n给体官能团的4-苯基噻唑基Ru（II）和Os（II）金属环的抗癌性能研究

制备了10个通式[M（对花香烃）thiCΛNMeIm]NO3的有机金属配合物（M = Ru, Os; MeIm = 1-甲基咪唑，thi = 4-苯基噻唑），它们在4-苯基噻唑支架上的取代基不同，并用标准分析方法对其进行了表征。在人肺腺癌（A549）、结肠腺癌（SW480）和人卵巢畸胎癌（CH1/PA-1）细胞系中研究了化合物的抗增殖活性。IC50值在低微摩尔范围内，有两个例外。此外，选定的化合物在HCT116结肠癌细胞系的2D（单层）和3D（多细胞球体）培养中测定了细胞毒性。对于选定的化合物，研究了在SW480细胞中诱导ROS的能力。细胞积累实验，以及稳定性和水溶液反应性的研究，为观察到的细胞毒性差异提供了结论性的解释。此外，进行了氨基酸和DNA相互作用的研究，以阐明作用机制的各个方面。对多细胞球体的抗增殖活性的深入了解迫使我们进行体内研究，揭示了体外无活性复合物的意想不到的治疗效果。

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来源期刊

Bioinorganic Chemistry and Applications 化学-生化与分子生物学

CiteScore

7.00

自引率

5.30%

发文量

105

审稿时长

>12 weeks

期刊介绍： Bioinorganic Chemistry and Applications is primarily devoted to original research papers, but also publishes review articles, editorials, and letter to the editor in the general field of bioinorganic chemistry and its applications. Its scope includes all aspects of bioinorganic chemistry, including bioorganometallic chemistry and applied bioinorganic chemistry. The journal welcomes papers relating to metalloenzymes and model compounds, metal-based drugs, biomaterials, biocatalysis and bioelectronics, metals in biology and medicine, metals toxicology and metals in the environment, metal interactions with biomolecules and spectroscopic applications.