Aim and Objective: C-Jun-N-terminal kinase -1 (JNK -1) is a
seriene/threonine kinase protein and a member of mitogen activated protein family
(MAP– Kinase). The activation of JNK-1 leads to cell proliferation, cell death, DNA
repair and metabolism. In our study we aim in creating a novel JNK-1 inhibitor.
Material and Method: Various computational techniques like 3D-atom based QSAR
analysis; pharmacophore based virtual screening; molecular docking and Density
functional theory approaches are utilised to obtain novel JNK-1 inhibitor.
Result: Pharmacophores with pharmacophoric features as two hydrogen bond
acceptors (A), one hydrogen bond donor (D), one hydrophobic (H) and one aromatic
ring (R) are generated. Amongst the generated pharmacophore hypothesis, AADHR.6
was found to have good survival score of 3.214 and is used to derive atom based 3D – QSAR model.
The obtained 3D – QSAR model has excellent squared correlation coefficient value (R2= 0.9272) and a
good fisher ratio (F= 273.9). The reliability and robustness of the chosen model is validated both
internally and externally to obtain good statistical results. The model AADHR.6 is used in virtual
screening of Zinc and NCI databases for potential inhibitors. Resulting hit compounds from virtual
screening are then subjected to docking and Density Functional Theory (DFT) studies.
Conclusion: Both docking and DFT studies brings out two lead compounds with good inhibitory
activity against the receptor. Thus the work presents a novel JNK – 1 inhibitor that can serve as
potential therapeutics for the treatment of various diseases associated with abnormal JNK -1