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Abstract

Androgenic hormones such as testosterone and dihydrotestosterone are essential for the progression of the prostate gland. Overexpression of androgenic receptors is responsible for the proliferation of prostate tumours and androgenic receptors are an essential target in prostate cancer therapy. Flutamide was the first Nonsteroidal androgen receptor antagonist used to treat prostate cancer, but it causes side effects such as hepatotoxicity. This study aims to develop less toxic compounds using a bioisosteric approach by replacing groups such as nitro, trifluoromethyl and aryl of Flutamide drug and to improve pharmacokinetic and toxicity prediction as well as docking studies of newly generated bioisosteres. The Lipinski rule of five was followed. In the docking study, docking scores were obtained in the range of -7.76 to -9.75 Kcal/mol. All ligands docked inside the binding pocket region share a shape that is complementary to the androgen receptor. Among the selected bioisosteres and flutamide, the common amino acid residue 746Val plays a key role in the activity and binding affinity. Based on their QED score, toxicity score, drug likeness, drug score, NR-AR score and binding scores with protein residue, compounds F3, F17, and F39 may be noble antiandrogen agents in the management of prostate cancer. INTRODUCTION:Throughout the world, cancer is a major cause of mortality and a leading obstacle to extending life expectancy. Worldwide, approximately 10 million deaths from cancer were reported, compared to 19.3 million cases in 2020. According to estimated data, there are approximately 1.4 million new prostate cancer (PC) patients diagnosed each year and 0.38 million deaths 1 .