Three-dimensional quantitative structure-activity relationship analysis of 37 6-azasteroids inhibitors was carried out by Topomer CoMFA. The new model’s cross validation and correlation coefficient were q2=0.774 and r2=0.965, respectively. The results show that the model has good prediction ability and reliability. Virtual screening based on Topomer search of ligand,virtual screening based on molecular docking of receptor and molecular activity prediction of 3D-QSAR model were applied to the new inhibitor grading screening. Finally, four new inhibitor compounds with high activity were obtained. The Surflex-dock results of new inhibitors showed that the interaction pattern between 6-azosterol inhibitors and 5α-reductaseⅡ target is mainly hydrogen bonding. The results of MTT assay showed that the new inhibitor could significantly inhibit the proliferation of BPH-1 cells and the degree of inhibition is concentration dependent. Molecular docking mechanism interpretation and prostatic growth inhibition assay in cytological experiments are mutually validated. It is proved that this virtual screening method can provide effective candidate compounds for the treatment of benign prostatic hyperplasia.
