Abstract
Procymidone (Similex®) is a fungicide with a weak anti-androgenic activity. The anti-androgenic activity and androgen receptor (AR)-binding activity of procymidone and its six metabolites were evaluated. Anti-androgenic activity was determined in HeLa cells transiently transfected with an AREx3-luciferase reporter and full-length human or rat AR expression vectors (anti-androgen assay). AR-binding activity was determined by a competitive ligand-binding assay based on a fluorescence polarization method (AR-binding assay). It was clear that procymidone, its hydroxylated metabolite (PCM–CH2OH), and their imide linkage-cleaved compounds (PCM–NH–COOH and PA–CH2OH) have anti-androgenic activity and AR-binding activity, and procymidone has the highest activity among these compounds. There were no differences between rats and humans regarding the activities of procymidone and the metabolites. The activity of procymidone was 20–70 times lower than that of hydroxyflutamide, which is a potent anti-androgen. The results indicate that the anti-androgenic activities of procymidone and its metabolites are very weak.
