QSAR Analysis of a Series of Hydantoin-based Androgen Receptor Modulators and Corresponding Binding Affinities

Androgen receptor (AR), a member of the nuclear hormone receptor superfamily of intracellular ligand-dependent transcription factors, plays an indispensable role in normal male development through the regulation of androgen through the binding with endogenous androgens. Inappropriate amounts of androgens have a severe adverse effect on men. Excessive androgen may contribute to accelerate prostatic hypertrophy, even prostate cancer, while the absence of androgen may result in reduced muscle mass and strength, decreased bone mass, low energy, diminished sexual function and an increased risk of osteoporosis and fracture. In these cases, androgen receptor modulators are important to maintain the normal biological function of AR. So androgen receptor modulators are necessary for human being to improve their happy life index. To explore the relationships between molecular structures and corresponding binding abilities to aid the new AR modulator design, multiple linear regressions (MLR) are employed to analyze a series of hydantoin analogues, which can bind to androgen receptor acting as AR modulators. The obtained optimum model presents wonderful reliabilities and strong predictive abilities with R² =0.858, $$ =0.822, $$ =0.813, $$ =0.840, $$ =0.807, $$ =0.814, CCC=0.893, respectively. The derived model can be used to predict the binding abilities of unknown chemicals and may help to design novel molecules with better AR affinity activity.