In silico and in vitro antioxidant and cytotoxicity evaluation of oxygenated xanthone derivatives

Many natural products play important roles as antioxidants and represent useful scaffolds for the development of new agents. Particularly, polyphenols in which oxygenated xanthones can be included have proven their efficacy as antioxidants for several applications. To better understand the antioxidant potential of oxygenated xanthones, a library of twenty mono and di-oxygenated xanthones was investigated. The antioxidant properties were evaluated by their 2,2-diphenyl-1-picrylhydrazyl (DPPH) and peroxyl radical scavenging effect as well as their inhibitory effect on the prooxidant enzyme myeloperoxidase (MPO). A quantitative structure-activity relationship (QSAR) model predicted the maximal atomic partial charge (Qmax) as the descriptor being implied in the antioxidant activity of the referred xanthones. From the antioxidant screening, emerged the hit compound, 1,2-dihydroxyxanthone (10), that was further characterized for its chelating properties and its effect on a human keratinocyte cell line. Taken together, the results suggest the possible effectiveness of xanthone derivatives as antioxidants with potential for topical administration. Keywords: Antioxidant activity, Myeloperoxidase, Scavenging effect, Structure-activity relationships, Xanthones