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Issue 12, 2005
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Synthesis, cytotoxicity, cellular uptake and influence on eicosanoid metabolism of cobalt–alkyne modified fructoses in comparison to auranofin and the cytotoxic COX inhibitor Co-ASS

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Abstract

Propargylhexacarbonyldicobalt complexes with fructopyranose ligands were prepared and investigated for cytotoxicity in the MCF-7 human breast cancer cell line. The antiproliferative effects depended on the presence of isopropylidene protecting groups in the carbohydrate ligand and correlated with the cellular concentration of the complexes. IC50 values of > 20 µM demonstrated that the fructose derivatives were only moderately active compared to the references auranofin and the aspirin (ASS) derivative [2-acetoxy(2-propynyl)benzoate]hexacarbonyldicobalt (Co-ASS). In continuation of our studies on the mode of action of cobalt–alkyne complexes we studied the influence of the compounds on the formation of 12-HHT (COX-1 product) and 12-HETE (12-LOX product) by human platelets as an indication of the interference in the eicosanoid metabolism, which is discussed as a target system of cytostatics. Co-ASS was an efficient COX-1 inhibitor without LOX inhibitory activity and auranofin inhibited both COX-1 and 12-LOX eicosanoid production. The missing activity of the fructopyranose complexes at the 12-LOX and the only moderate effects at COX-1 indicate that COX/LOX inhibition may be in part responsible for the pharmacological effects of auranofin and Co-ASS but not for those of the fructopyranose complexes.

Graphical abstract: Synthesis, cytotoxicity, cellular uptake and influence on eicosanoid metabolism of cobalt–alkyne modified fructoses in comparison to auranofin and the cytotoxic COX inhibitor Co-ASS

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Publication details

The article was received on 24 Mar 2005, accepted on 06 May 2005 and first published on 25 May 2005


Article type: Paper
DOI: 10.1039/B504294C
Org. Biomol. Chem., 2005,3, 2282-2286

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    Synthesis, cytotoxicity, cellular uptake and influence on eicosanoid metabolism of cobalt–alkyne modified fructoses in comparison to auranofin and the cytotoxic COX inhibitor Co-ASS

    I. Ott, T. Koch, H. Shorafa, Z. Bai, D. Poeckel, D. Steinhilber and R. Gust, Org. Biomol. Chem., 2005, 3, 2282
    DOI: 10.1039/B504294C

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