MOLECULAR DOCKING INTERACTION STUDY OF BROMOPHENOLS ISOLATED FROM POLYSIPHONIA SPECIES A RED SEAWEED ON THE KEAP1-KELCH DOMAIN AS FREE RADICAL SCAVENGERS

Abstract

Several bromophenolic compounds from Polysiphonia species across the world have been isolated and structurally elucidated, and their free radical scavenging activity was proven by the DPPH method. Free radicals are formed due to the oxidative stress that the human body suffers due to several reasons. The NRF2 protein system acts as a principal transcription factor that functions as the body's primary protector against oxidative stress. But during unstressed conditions, NRF2 is regulated by its inhibitor, KEAP1 (Kelch-like ECH-associated protein 1). KEAP1 functions as a detector, perpetually attaching to NRF2 and designating it for elimination by the cell's "recycling mechanism." If this protein-protein interaction can be inhibited by small molecule inhibitors, then the body’s free radical scavenging potential can remain switched on, and the body can be freed from this harmful free radical. Herein, we have reported the molecular docking study of seventeen compounds (CPD-1 through CPD-17) as polybromophenolic compounds having DPPH activity mentioned as IC50 (in µM). AutoDock tools along with CB-Dock2 were employed for docking interaction studies, and four compounds (CPD-16, 10, 14, and 1) were chosen as good hits for this study. The non-bonded interaction studies have identified CPD-16 as the best result, which outperforms in silico data with that of the co-crystallized compound. The binding affinity was found to be -11.0 kcal/mol and has all the crucial interactions with the amino acid residues of the target protein. The common feature pharmacophore implies that the number and position of the bromine atoms in the compounds are crucial along with the scaffold type that hogs the active site of the protein.