In Silico Design and Molecular Docking Study of Some Novel Flutamide Analogues in the Management of Prostate Cancer

The androgen receptor (AR) plays a crucial role in the development of sexual functions in men, as well as the overexpression of androgenic hormones that contribute to prostate cancer (PC) development. Therefore, AR is an essential target for PC research. The aryl group of flutamide has been used as a replacement site in the present study to design newer and safer analogues using a bioisosteric approach with reduced toxicity. To design flutamide analogues, MolOpt was used along with ADMETlab 2.0 to determine their pharmacokinetic and toxicity properties. Additionally, OSIRIS Property Explorer was used to eliminate drug-likeness and drug score. Docking of the newly designed analogues was carried out using ArgusLab 4.0.1 based on Hartree–Fock calculations. The docking score ranged from –8.12 to –11.06 kcal/mol for all the ligands. A good binding score was observed for ligands 008, 009, 012, 016, 018 and 020, which had significantly better binding features than the other ones. Results from the in silico approaches (docking and ADMET study) suggest that these compounds 008 and 020 may have the potential as anti-androgen for prostate cancer. The hypothesis may be tested by synthesizing and evaluating the compounds for anti-androgen activity using in vitro and in vivo appro­aches.