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 x 10(-6) M), which was one order of magnitude greater than that of the corresponding lead compound tert-butylhydroxy-anisole (BHA) (IC50 1.04 x 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.
Ferrini
Serena
S
Dipartimento di Chimica, Università di Siena, via A. Moro 2, Siena, I-53100 Italy.
Fusi
Stefania
S
Ponticelli
Fabio
F
Valoti
Massimo
M
D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
C523236:2-tert-butyl-4-(4-phenyl-isoxazol-3-ylmethoxy)-phenol; D000975:Antioxidants; D016166:Free Radical Scavengers; D006571:Heterocyclic Compounds; D007555:Isoxazoles; D010636:Phenols