Heteroaryl-substituted phenols as potential antioxidants

A series of O-heteroaryl phenols have been synthesised and structurally characterised. Photo-Fries rearrangement of these compounds represents a useful way to access the corresponding C-heteroaryl derivatives. The activity of the new phenolic compounds as radical scavengers towards the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS+•) has been evaluated. 2-tert-Butyl-4-(4-phenyl-isoxazol-3-ylmethoxy)-phenol (compound 3c) showed the highest scavenger activity (IC50 value (i.e. the concentration that scavenged 50% of the radicals) 3.17 × 10-6 M), which was one order of magnitude greater than that of the corresponding lead compound tert-butylhydroxy-anisole (BHA) (IC50 1.04 × 10-5 M). In further experiments, compound 3c showed dose-dependent inhibition of the oxidation of linoleic acid, as well as methaemoglobin formation, promoted by the presence of the radical generator 2,2′-azobis(amidino-propane) hydrochloride (AAPH) and it was markedly more potent than BHA in these assays. © 2007 The Authors.