title: 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.
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. IC(50) values of > 20 microM 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.
authors: Institute of Pharmacy, Free University of Berlin, Königin-Luise-Str. 2 + 4, 14195 Berlin, Germany.
authors: Ingo
authors: I
authors: Ott
authors: Thao
authors: T
authors: Koch
authors: Hashem
authors: H
authors: Shorafa
authors: Zhenlin
authors: Z
authors: Bai
authors: Daniel
authors: D
authors: Poeckel
authors: Dieter
authors: D
authors: Steinhilber
authors: Ronald
authors: R
authors: Gust
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001310:Auranofin / Q000737:chemistry*; D003035:Cobalt / Q000737:chemistry*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015777:Eicosanoids / Q000378:metabolism*; D005632:Fructose / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared
chemical_list: D000480:Alkynes; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D005632:Fructose; D003035:Cobalt; D001310:Auranofin