Design of potent human steroid 5α-reductase inhibitors: 3D-QSAR CoMFA, CoMSIA and docking studies

3D-QSAR CoMFA, CoMSIA and docking studies were performed on a set of 4-azasteroidal human steroid 5 alpha-reductase inhibitors. The models developed using maximal common substructure-based alignment was found to be reliable and significant with good predictive r (2) value. CoMSIA model developed using combination of steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor features has shown r (cv) (2) = 0.564 with six optimum components, r (ncv) (2) = 0.945, F value = 101.196, r (Pred) (2) = 0.693 and SEE = 0.209. The contour plots obtained has shown a favourable effect of bulkier groups at C-17 position. Docking studies indicates the importance of bulkier groups at C-17 position for favourable activity. The study further helps in design of potent inhibitors of the enzyme.