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 (2 E )-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. Communicated by Ramaswamy H. Sarma.