The antioxidant activity of tetrahydrofuran lignans from Anogeissus rivularis: theoretical insights into the radical scavenging activity and enzyme inhibition

Novel tetrahydrofuran lignans (HFL) identified from Anogeissus rivularis showed potential antioxidant effects in previous studies, increasing the possibility of modifying these substances for medicinal use in illnesses associated with oxidative stress. A detailed analysis of the antioxidant activity of these compounds is therefore beneficial for medical uses. The capability of four HFL variants to scavenge radicals in polar (water at pH = 7.40) and nonpolar (gas phase and pentyl ethanoate) media was examined in this work employing kinetic and thermodynamic models. The hydroperoxyl radical trapping activity of HFL with the overall rate constants of 10(5)-10(7) M-1 s(-1) is faster in polar than in nonpolar media. In nonpolar environments, the FHT pathway is primarily responsible for the activity of these HFL; however, in the aqueous solution, the SET pathway is favored. According to the computed data, the hydroperoxyl radical trapping activity of HFL in the studied environments follows the order 2 > 3 similar to 4 > 1. In particular, the scavenging of HOO center dot radicals by compound 2 is roughly 16 and 100 times greater in lipid and aqueous media, respectively, than the activity of Trolox in the same. Considering a parallel antioxidant pathway via inhibiting free radical producing enzymes, docking analysis revealed that the investigated compounds also have a strong affinity for the CP450, MP, and NO enzymes, exhibiting favorable interactions with key amino acid residues. Thus tetrahydrofuran lignan 2 is a promising natural antioxidant in physiological environments.