ABSTRACT

Background:Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths globally.The Nrf2/Keap1 signaling pathway is one of the most important for cell defense against xenobiotics and oxidative stress. Nrf2 is found to regulate the anticancer effect of a number of cytoprotective drugs, and also contributes to the growth of cancer.Therefore, it makes obvious that both of the Nrf2 agonists and antagonists could be utilised to treat cancer.Numerous spices and their bioactive components have been employed as healing herbs in folk medicine to cure a range of illnesses. Aim: Our aim of the study lies on searching potent anticancer therapeutic agent as a form of spice bioactive compound via analysing through various computational tools including molecular docking. Methods: The docking process was initiated by retrieving the three dimensional structure of protein molecule (human Nrf2 protein complex 2FLU) from RCSB-PDB database and the ligand molecules (bioactive compounds) from PubChem database. Next, structure preparation and docking was carried out by the AutoDock Vina, and finally, binding affinity of the protein-ligand complxes were analysed and the stability of the docked complexes was verified via dynamics simulation.Furthermore, different toxicity software was used for the determination of toxicity and Pharmacokinetic properties of the bioactive molecules to understand their suitability drug development. Results: Among all the bioactive compounds, piperine from black pepper show the highest binding affinity (-8.7 kCal/mol.) with the target protein. All other compounds obey Lipinski’s rule of 5 and have the potency to be applied as a future anti-cancer drug candidate. Conclusion: Based on computational study, it can be concluded that Indian ethnic spices harbour many bioactive compounds that may be used in future cancer drug development