Inhibition of Oxidation of Low-Density Lipoprotein by a Novel Antioxidant, BO-653, Prepared by Theoretical Design

2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butyl-benzofuran (BO-653) is a novel antioxidant synthesized by theoretical designing based on the previous experimental findings and consideration. The antioxidant activities of BO-653 against the oxidative modification of low-density lipoprotein (LDL) induced by free radicals were studied. BO-653 was consumed faster than endogenous α-tocopherol and inhibited the formation of lipid hydroperoxides, which was observed during the consumption of α-tocopherol. Doxyl stearic acids incorporated into LDL as spin probes competed with the antioxidants in scavenging radicals. It was found that the efficacy of radical scavenging by α-tocopherol became smaller as the radical went deeper into the interior of LDL particle, whereas that by BO-653 did not change. Ascorbic acid in the aqueous phase spared α-tocopherol efficiently during oxidation. On the other hand, the sparing effect of ascorbic acid for BO-653 was not remarkable, unlike that for α-tocopherol, which implied different locations of radicals derived from BO-653 and α-tocopherol within the LDL particle. It was concluded that BO-653 protected LDL from oxidative modification efficiently by scavenging peroxyl radicals and by reducing α-tocopheroxyl radicals and that this novel antioxidant might act as a potent inhibitor of development of atherosclerosis.