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.
Keyphrases
- molecular dynamics
- molecular docking
- crystal structure
- prostate cancer
- density functional theory
- high resolution
- radical prostatectomy
- cell proliferation
- molecular dynamics simulations
- ionic liquid
- poor prognosis
- binding protein
- genome wide
- nucleic acid
- long non coding rna
- gene expression
- risk assessment
- magnetic resonance imaging
- pi k akt
- climate change
- human health
- dna binding
- dna methylation
- smoking cessation