Carboxymethylnaringenin: a promising antioxidant in the aqueous physiological environment

The synthetic naringenin derivative (2S)-8-carboxymethylnaringenin (<b>CMN</b>) was developed for the treatment of bacterial and viral respiratory infections. There are indications that <b>CMN</b> may act as an antioxidant, however, no studies have been conducted in this regard. This work is aimed at assessing the antiradical capacity of <b>CMN</b> against various physiologically relevant species in physiological environments by using thermodynamic and kinetic calculations. According to the results, <b>CMN</b> only exhibits modest HOO^• antiradical activity in lipid medium, modeled here as pentyl ethanoate solvent, with an overall rate constant (<i>k</i>_overall) of 2.01 × 10² M^-1 s^-1. However, significant antiradical activity is predicted for the aqueous medium (<i>k</i>_overall = 2.60 × 10⁵ M^-1s^-1) that is equivalent to the activity of the reference antioxidant Trolox. In a screen performed on a range of radicals, HO^•, NO₂, SO₄^•-, N₃^•, CH₃O^•, CCl₃O^•, CH₃OO^•, and CCl₃OO^• were also successfully scavenged by <b>CMN</b> in water at physiological pH. Therefore, other than a potent drug, <b>CMN</b> is also a good antioxidant in polar environments.