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Chemical Structure| 36097-48-0

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Getreuer, Paul ; Mendrina, Theresa ; Terwingen, Steven van ; Marretta, Laura ; Dömötör, Orsolya ; Wenisch, Dominik , et al.

Abstract: Ten organometallic complexes of the general formula [M(p-cymene)thiCΛNMeIm]NO3 (M = Ru, Os; MeIm = , 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 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.

Keywords: 2D & 3D cytotoxicity ; anticancer ; C,N-chelates ; in vivo studies ; leaving group variation ; metallacycles ; metallodrugs

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Paul Getreuer ; Laura Marretta ; Emine Toyoglu ; Orsolya Dömötör ; Michaela Hejl ; Alexander Prado-Roller , et al.

Abstract: In this contribution we report the synthesis, characterization and in vitro anticancer activity of novel cyclometalated 4-phenylthiazole-derived ruthenium(II) (2a–e) and osmium(II) (3a–e) complexes. Formation and sufficient purity of the complexes were unambigiously confirmed by 1H-, 13C- and 2D-NMR techniques, X-ray diffractometry, HRMS and elemental analysis. The binding preferences of these cyclometalates to selected amino acids and to DNA models including structures were analyzed. Additionally, their stability and behaviour in aqueous solutions was determined by UV-Vis spectroscopy. Their cellular accumulation, their ability of inducing , as well as their interference in the were studied in SW480 colon cancer cells. The anticancer potencies were investigated in three human cancer cell lines and revealed IC50 values in the low micromolar range, in contrast to the biologically inactive ligands.

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Product Details of [ 36097-48-0 ]

CAS No. :36097-48-0
Formula : C9H13N3O3
M.W : 211.22
SMILES Code : O=C(OC)[C@@H](NC(C)=O)CC1=CNC=N1
MDL No. :MFCD00237490

Safety of [ 36097-48-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338
 

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