Ligand Based Pharmacophore Model Development for Anti Androgen Receptor Drugs for Treating Prostate Cancer

The computational modeling and high throughput screening techniques have been used to identify small molecules that specifically target functional surface sites of the androgen receptor in Prostate cancer. Pharmacophore modeling, Virtual screening, docking based analyses is used for development of new chemical entities. The purpose of the current work is to establish pharmacophore model for the FDA approved anti-androgen receptor drugs of prostate cancer by using the software Ligand Scout 3.1, The data sets for the anti-androgen compounds were downloaded in.sdf format from Pubchem database. The model consists of five hydrogen bond acceptors, and one hydrophobic moieties and one aromatic ring which are defined as essential feature for androgen receptor inhibitors. Then the derived pharmacophore model was compared with the Zinc database of available standard anticancer drugs, Virtual screening of ZINC chemical databases leads to identification of one hit, and this compound can be useful for the design of future targets and development of new drugs to cancer. The newly obtained compound is then docked with androgen receptor with the help of Autodock Vina 4.0.The result obtained from the present study suggests that the application of ligand based pharmacophore could assist in selection of potential leads for rational design of androgen receptor inhibitors in prostate cancer therapy. INTRODUCTION: Prostate cancer is predicted to be the leading cause of cancer-related death in men over the next decade 1 . In its early stages and when localized to the prostate, this cancer can usually be cured by surgery or radiation therapy. However, for advanced, metastatic or recurrent disease, alternative systemic treatments are required. In this regard, the androgen receptor, a ligand-inducible transcription factor, is considered to be central for Prostate cancer development, growth and metastasis 2 .