Computational insights on the antioxidant, antinitrosant, and xanthine oxidase inhibitory capacities of neobavaisoflavone

Neobavaisoflavone (Neo) is a prenylated isoflavone-type compound found in several plant species, including Psoralea corylifolia. It has been reported to exhibit a wide range of health benefits, notably anti-inflammatory and anti-cancer properties. In the present study, the antioxidant and antinitrosant activities as well as the xanthine oxidase (XO) inhibitory capacity of Neo have been systematically investigated using computational approaches. The antioxidant and antinitrosant potencies were evaluated by modeling the chemical reactions of Neo with hydroperoxyl radical (HOO) and nitrogen dioxide (NO2) as model radicals under physiological conditions. The XO inhibitory capacity was evaluated using a blind docking consensus approach and molecular dynamic simulations. The findings indicate that Neo is a very good scavenger of both HOO and NO2 in water through the SPLET (sequential proton loss electron transfer) mechanism, while it is a moderate scavenger in lipid media via the FHT (formal hydrogen transfer) mechanism. The kinetic study revealed that the 14-OH group is the most favorable site for free radical attack, despite the thermodynamic preference of the 17-CH group. The overall reaction rate coefficient of Neo in water was found to be higher than that of Trolox and BHT for scavenging HOO and comparable to that of syringic acid for scavenging NO2. Consequently, Neo is a promising radical scavenger in physiological polar media. On the other hand, Neo was expected to be a good inhibitor of XO, inhibiting the same pathway as quercetin.