Anti-androgen activity of polybrominated diphenyl ethers determined by comparative molecular similarity indices and molecular docking

Some polybrominated diphenyl ethers (PBDEs) may have endocrine-disrupting (ED) potencies. In this study, molecular docking and three-dimensional quantitative structure–activity relationship (3D-QSAR) were performed to explore the possible anti-androgenicity of PBDEs. Based on the alignment generated by docking conformations, a highly predictive comparative molecular similarity indices analysis (CoMSIA) model was developed with q2 value of 0.642 and r2 value of 0.973. The contributions of the steric, electrostatic, hydrophobic fields to the CoMSIA model are 13.1%, 61.0% and 25.9%, respectively. Br substitutions which are at meta and para positions of PBDEs will be unfavorable for androgen receptor (AR) antagonism and ortho Br substitutions for PBDEs are favorable for anti-androgen activity. Mapping the 3D-QSAR models to the active site of the AR provides new insight into the AR–PBDEs interaction. CoMSIA field contributions showed good consistency with structural features of the AR binding site and can be used to predict anti-androgen activities of other PBDE congeners.