In silico nbsp Identification of potential alpha ndash reductase inhibitors for prostatic diseases QSAR modelling molecular docking and pre ADME predictions

Background Benign Prostatic Hyperplasia and prostate cancer are some of the most common old age men diseases and caused by augmented level of potent androgen dihydrotestosterone DHT Preventing DHT synthesis via alpha reductase AR inhibition has been shown to have a remarkable effect on prostatic disease with low toxicity Thus there is much interest in the potential role for AR inhibitors ARIs in the management of prostatic diseases Some of the natural products semi synthetic derivatives especially steroidal molecules are effective inhibitors of AR However given the limited number of clinically approved inhibitors and the associated side effects the discovery of new inhibitors is urgent Here the In silico approaches have been performed to identify new potential inhibitors of AR Methods In the present study two and three dimensional D and D QSAR models have been developed using a selected series of steroidal derivatives as ARIs in order to elucidate the structural properties required for alpha Reductase AR inhibitory activity and anticancer activity Further In silicostudies molecular docking and pre ADME of selected series have also been carried out to identify the binding orientation and the receptor ligand interactions responsible for exhibited activity and the drug like properties Results Best D QSAR model was generated using Simulated Annealing Partial Least Square SA PLS method r q F value and pred r whereas simulated annealing k nearest neighbor SA kNN approach provided us with best D QSAR model q and pred r The compounds were further sorted by applying ADME properties against prostate cancer cell lines PC Docking analysis indicated that the selected series of compounds have comparable binding affinity with the receptor protein and suggested that hydrophobic and electrostatic moieties can have a key role in the inhibition mechanism These findings can provide a new strategy to develop new steroidal ARIs useful in prostatic disease