2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran: Design and Evaluation as a Novel Radical-Scavenging Antioxidant against Lipid Peroxidation

• Published in: Archives of biochemistry and biophysics Vol. 342; no. 2; pp. 236 - 243
• Main Authors: Noguchi, Noriko, Iwaki, Yoshihide, Takahashi, Mareyuki, Komuro, Erika, Kato, Yoshiaki, Tamura, Kunio, Cynshi, Osamu, Kodama, Tatsuhiko, Niki, Etsuo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-06-1997
• Subjects: antioxidant; antioxidantes; antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; antioxydant; Ascorbic Acid - metabolism; Ascorbic Acid - pharmacology; Azo Compounds - metabolism; Benzhydryl Compounds - metabolism; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Chromatography, High Pressure Liquid; compose phenolique; compuestos fenolicos; Drug Design; Electron Spin Resonance Spectroscopy; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; free radicals; Kinetics; Linoleic Acids - metabolism; lipid peroxidation; Lipid Peroxidation - drug effects; Liposomes - metabolism; Molecular Structure; Nitriles - metabolism; Oxidation-Reduction; peroxidacion lipidica; Peroxides - metabolism; peroxydation des lipides; phenolic compounds; Phenols - metabolism; Phosphatidylcholines - metabolism; radical libre; radicales libres; Spin Labels; Vitamin E - metabolism; Vitamin E - pharmacology; α-tocopherol; antioxidant; free radicals; lipid peroxidation; α-tocopherol
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.1997.9994

To develop a novel potent radical-scavenging antioxidant, the ideal structure of a phenolic compound was designed considering the factors that determine antioxidant potency. 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653) was thus synthesized and its antioxidant activity was evaluated against lipid peroxidationsin vitro.The electron spin resonance study showed that the phenoxyl radical derived from BO-653 was more stable than α-tocopheroxyl radical. BO-653 reduced α-tocopheroxyl radical rapidly, but α-tocopherol did not reduce the phenoxyl radical derived from BO-653. However, the chemical reactivity of BO-653 toward peroxyl radical was smaller than that of α-tocopherol. This was interpreted as the steric effect of bulkytert-butyl groups at bothorthopositions which hindered the access of peroxyl radical to the phenolic hydrogen. However, thetert-butyl substituents increased the stability of BO-653 radical and also lipophilicity, and its antioxidant potency against lipid peroxidation in phosphatidylcholine liposomal membranes was superior to that of α-tocopherol. Ascorbic acid reduced the phenoxyl radical derived from BO-653 and spared BO-653 during the oxidation of lipid in the homogeneous solution. On the other hand, ascorbic acid did not spare BO-653 in the oxidation of liposomal membranes. It was concluded that BO-653 is a potent novel radical-scavenging antioxidant.