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
{"title":"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","authors":"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","doi":"10.1155/bca/6352081","DOIUrl":null,"url":null,"abstract":"<p><p>Ten organometallic complexes of the general formula [M(<i>p</i>-cymene)thi<sub>CΛN</sub>MeIm]NO<sub>3</sub> (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<sub>50</sub> 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.</p>","PeriodicalId":8914,"journal":{"name":"Bioinorganic Chemistry and Applications","volume":"2025 ","pages":"6352081"},"PeriodicalIF":4.1000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463534/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring the Anticancer Properties of 4-Phenylthiazole-Based Ru(II) and Os(II) Metallacycles Featuring 1-Methylimidazole as <i>N</i>-Donor Functionality.\",\"authors\":\"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\",\"doi\":\"10.1155/bca/6352081\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ten organometallic complexes of the general formula [M(<i>p</i>-cymene)thi<sub>CΛN</sub>MeIm]NO<sub>3</sub> (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<sub>50</sub> 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. 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Exploring the Anticancer Properties of 4-Phenylthiazole-Based Ru(II) and Os(II) Metallacycles Featuring 1-Methylimidazole as N-Donor Functionality.
Ten organometallic complexes of the general formula [M(p-cymene)thiCΛNMeIm]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.
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.
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