Crystal structure determination, molecular docking, and molecular dynamics of arylal dimedones as potential inhibitors for castrate‐resistant prostate cancer

Increased androgen receptor (AR) signaling brought on by higher intratumoral androgen production and AR amplification is associated with castrate‐resistant prostate cancer (CRPC). Cell proliferation in this case continues even during low expression of testosterone in the body. Aldo‐keto reductase family 1 member C3 (AKR1C3) is one of the most elevated genes in CRPC and catalyzes the formation of powerful AR ligands from inactive forms. The current work aimed to use the x‐ray method to investigate the ligand's crystal structure while also conducting molecular docking and molecular dynamics tests on the synthesized molecules against AKR1C3. As per the results obtained, the MM‐PBSA binding energies of inhibitors 2,2'‐((4‐methoxyphenyl)methylene)bis(3,4‐hydroxy‐5,5‐dimethylcyclohex‐2‐en‐1‐one is −132.456 kJ mol−1 and 2,2'‐(phenylmethylene)bis(3‐hydroxy‐5,5‐dimethylcyclohex‐2‐en‐1‐one is −81.017 kJ mol−1. These results create a promising approach to drug design based on its fit to the structures of the receptor site rather than basing it on analogies to other active structures.