Free Radical Scavenger Activity and P-glycoprotein Inhibition Capacity of 1,2,4-Trihydroxyxanthone

Abstract

Some xanthone derivatives isolated from plants possess antifungal, antimicrobial, antioxidative and cytotoxic activities. Therefore, products manufactured from plants that contain xanthones are used as botanical dietary supplements. The operative mechanism of antioxidative action of 1,2,4-trihydroxyxanthone is investigated in this contribution. For this purpose, M06-2X/6-311++G(d,p) method is used. Antioxidative capacity of investigated xanthone is determined in benzene and water as mediums. It is found that, among three possible radicals that this xanthone can generate, the most stable is the one obtained by homolytic cleavage of O-H group in position 4. It was found that HAT (Hydrogen Atom Transfer) is the only operative mechanism for xanthone in benzene. On the other hand, the most favorable mechanism in water is SPLET (Sequential Proton Loss Electron Transfer). It should be emphasized that SET-PT (Single-Electron Transfer followed by Proton Transfer) is not plausible mechanistic pathway in both solvents. Antioxidants express their scavenger capacity in the presence of free radicals. Therefore here is examined scavenger capacity of 1,2,4-trihydroxyxanthone toward HO\\( ^{\\bullet}\\), HOO\\( ^{\\bullet}\\) and CH3OO\\( ^{\\bullet}\\) radicals. It is found that the investigated xanthone is able to deactivate free radicals via competitive HAT and SPLET mechanisms. The observed reactivity of the xanthone toward free radicals decreases following the order: HO\\( ^{\\bullet}\\) ≫ HOO\\( ^{\\bullet}\\) > CH3OO\\( ^{\\bullet}\\). It should be pointed out that reactivity of the xanthone to selected free radicals slightly increases with an increase in solvent polarity.