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

Abstract

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 -132.456kJmol-1 and 2,2'-(phenylmethylene)bis(3-hydroxy-5,5-dimethylcyclohex-2-en-1-one is -81.017kJmol-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.