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

Getreuer, Paul and Mendrina, Theresa and Terwingen, Steven van and Marretta, Laura and Dömötör, Orsolya and Wenisch, Dominik and Hejl, Michaela and Heffeter, Petra and Berger, Walter and Jakupec, Michael A. and Terenzi, Alessio and Keppler, Bernhard K. and Kandioller, Wolfgang (2025) Exploring the Anticancer Properties of 4‐Phenylthiazole‐Based Ru(II) and Os(II) Metallacycles Featuring 1‐Methylimidazole as N ‐Donor Functionality. BIOINORGANIC CHEMISTRY AND APPLICATIONS, 2025 (1). No. 6352081. ISSN 1565-3633

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Abstract

Ten organometallic complexes of the general formula [M( p ‐cymene)thi CΛN MeIm]NO 3 (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. IC 50 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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