నైరూప్య

Insights into interaction profile and inhibitory potential of amentoflavone with ?-glucosidase, tyrosinase and 15-lipoxygenase as validated therapeutic targets.

Tomisin Happy Ogunwa

Therapeutic benefits of amentoflavone, a 5',8"-biapigenin isolated from numerous medicinal plants, in the management of human ailments has been reported. However, the mechanisms of action and precise interaction of this biflavonoid with protein targets for such bioactivities have not been exhaustively documented. The present study shows the first binding model of amentoflavone with few selected human proteins (α-glucosidase, tyrosinase and 15-lipoxygenase) as validated therapeutic targets using computational procedures. Results obtained divulged amentoflavone interference with the metal ions within the active site of tyrosinase and lipoxygenase as part of its inhibitory mechanism against the proteins. The predicted inhibitory potential of the biflavonoid against 15-lipoxygenase correlates with IC50 value (0.04 µM). Its binding poses were comparable to that of acarbose on α-glucosidase with highest affinity (-11.4 kcal/mol) while the modest affinity (-9.4 kcal/mol) for tyrosinase indicates moderate inhibition for the compound possibly due to its interaction with only one of the two copper ions. It was observed that amentoflavone stably occupied the active sites of all the proteins with lesser ?G values and engaged one of its monoflavonoid subunits for penetration into binding pocket, preventing substrate access, binding and conversion. However, the relatively bulky structure of amentoflavone was prone to steric hindrance within the binding pockets. The polyhyroxyl groups of the biflavonoid participate critically in the formation of hydrophilic interaction. The aromatic rings enjoyed hydrophobic interactions with residues side chain and π-π stacking with the phenolic rings of aromatic amino acids. The unique binding configurations and interactions obtained against each protein in this study may be helpful in explaining the subtle differences of the biflavonoid potency (IC50 values). The data also validate amentoflavone as a useful candidate in treatment of diabetes, inflammation and hyperpigmentary disorders.