title: Peroxidase-mediated in vitro metabolism of diethylstilbestrol and structural analogs with different biological activities.
abstract: The comparative peroxidative metabolism of diethylstilbestrol (DES) and structurally related compounds of different biological activity was investigated in vitro with horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) as a model peroxidase system: UV spectroscopy revealed the formation of p-quinone intermediates in HRP-H2O2 catalyzed incubations of DES, 3',3",5',5"-tetrafluoro-DES (TF-DES) and dimethylstilbestrol (DMS) and the tautomerization of the quinones to their dien compounds, Z,Z-dienestrol (Z,Z-DIES), tetrafluoro-dienestrol (TF-DIES) and dienmestrol (DIMS) respectively, which were characterized by HPLC and GC/MS. Z,Z-DIES, E,E-DIES, TF-DIES and DIMS were subject to further peroxidative metabolism; however, quinone intermediates were not formed in the HRP-H2O2 containing incubations according to UV spectroscopy. Similarly, hexestrol (HES), 4'-O-methyl-DES (M-DES) and 4',4"-O-dimethyl-DES (DM-DES) did not form quinone intermediates; moreover, they showed little or no apparent metabolic conversion under conditions where DES, TF-DES and DMS were readily peroxidized. However, at a 20-fold higher peroxidase concentration HES and M-DES showed metabolic conversion whereas DM-DES did not.
mesh_terms: D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004054:Diethylstilbestrol / Q000031:analogs & derivatives* / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008954:Models, Biological; D010544:Peroxidases / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D014316:Tritium; D004054:Diethylstilbestrol; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D010544:Peroxidases