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.

Crystal structure determination, molecular docking and dynamics of arylidene cyanoacetates as potential JNK-3 inhibitors for Ischemia reperfusion injury.

Ischemia reperfusion injury is a cardiovascular condition which causes hypoxia by means of obstruction of arterial blood flow eventually leads to reduced synthesis of adenosine tri-phosphate in the mitochondria. c-Jun N-terminal kinase-3 are related to several cascade of events like apoptosis, oxidative stress and mitochondrial dysfunction which can be further related to Ischemia-reperfusion injury. The present study was aimed at determining crystal structure of the ligand by x-ray methods and to perform molecular docking and molecular dynamics studies of the arylidene cyano-acetates with c-Jun N-terminal kinase-3. The binding energy of Ethyl (2E)-2-cyano-3-(4-methoxyphenyl)prop-2-enoate is -4.462 kcal/mol and ethyl (2E)-2-cyano-3-phenylprop-2-enoate is -6.135 kcal/mol. This has created a new rational approach to drug design, where the structure of drug is designed, based on its fit to structures of receptor site, rather than basing it on analogies to other active structures. The above compounds are binding strongly with c-Jun N-terminal kinase-3 protein.[Figure: see text]Communicated by Ramaswamy H. Sarma.