Reaction with ROO• and HOO• Radicals of Honokiol-Related Neolignan Antioxidants

Honokiol is a natural bisphenol neolignan present in the bark of Magnolia officinalis, whose extracts have been employed in oriental medicine to treat several disorders, showing a variety of biological properties, including antitumor activity, potentially related to radical scavenging. Six bisphenol neolignans with structural motifs related to the natural bioactive honokiol were synthesized. Their chain-breaking antioxidant activity was evaluated in the presence of peroxyl (ROO center dot) and hydroperoxyl (HOO center dot) radicals by both experimental and computational methods. Depending on the number and position of the hydroxyl and alkyl groups present on the molecules, these derivatives are more or less effective than the reference natural compound. The rate constant of the reaction with ROO center dot radicals for compound 7 is two orders of magnitude greater than that of honokiol. Moreover, for compounds displaying quinonic oxidized forms, we demonstrate that the addition of 1,4 cyclohexadiene, able to generate HOO center dot radicals, restores their antioxidant activity, because of the reducing capability of the HOO center dot radicals. The antioxidant activity of the oxidized compounds in combination with 1,4-cyclohexadiene is, in some cases, greater than that found for the starting compounds towards the peroxyl radicals. This synergy can be applied to maximize the performances of these new bisphenol neolignans.

Automated summary

Six bisphenol neolignans were synthesized and their antioxidant activity was evaluated. The derivatives showed varying effectiveness compared to the natural compound, depending on the presence and position of hydroxyl and alkyl groups. Compound 7 exhibited a significantly higher reaction rate with ROO• radicals than honokiol. The addition of 1,4-cyclohexadiene restored the antioxidant activity of compounds with quinonic oxidized forms by generating HOO• radicals. The combination of oxidized compounds with 1,4-cyclohexadiene showed increased antioxidant activity in some cases.