Computational Profile of Novel Natural Bioactive Inhibitors of NF-κB

Abstract

Nuclear factor-κB (NF-κB) represents a family of inducible transcription factors, which regulates a large array of genes involved in different processes of the immune and inflammatory responses. Deregulated NF-κB activation contributes to the pathogenic process of various diseases such as inflammation and cancer. NF-κB signaling in cancer cells is involved in cellular proliferation, angiogenesis, invasion, metastasis, development of drug resistance and anti-apoptosis. Objective: To identify potent NF-κB and IκBα inhibitors using molecular docking study. Methods: Proteins and ligands were prepared from Pymol and AutoDock vina and results were visualized by using Discovery studio visualizer. Results: Natural bioactive compounds such as Brevilin A, Tagitinin E, Japonicone G and Hiyodorilactone A were targeted on NF-κB and IκBα. The docking score of the Brevilin A, Tagitinin E, Japonicone G and Hiyodorilactone A with NF-κB were -9.8Kcal/mol, -10.1Kcal/mol, -11.9Kcal/mol, and - 8.4Kcal/mol respectively. The docking score of the Brevilin A, Tagitinin E, Japonicone G and Hiyodorilactone A with IκBα were -7.1Kcal/mol, -7.0Kcal/mol, -8.8Kcal/mol and -6.8Kcal/mol respectively. Control group (JSH-23 synthetic inhibitor) showed -6.5Kcal/mol and -5.5Kcal/mol with NF-κB and IκBα respectively. Conclusions: The present study reflects that Brevilin A, Tagitinin E, Japonicone G and Hiyodorilactone A show promising results as a crucial drug target in NF-κB signaling cascade. However, to validate the inhibitory activity of these ligands further in-vitro analysis are suggested to develop novel anti-inflammatory/anti-cancer drugs.