Peroxidase-mediated in vitro metabolism of diethylstilbestrol and structural analogs with different biological activities.

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.