普罗布考
化学
自动氧化
维生素E
脂质过氧化
低密度脂蛋白
体内
亚油酸
脂蛋白
维生素C
体外
维生素
药理学
抗氧化剂
生物化学
立体化学
胆固醇
脂肪酸
医学
生物技术
生物
作者
Kunio Tamura,Yoshiaki Kato,Akira Ishikawa,Yasuharu Kato,Motomu Himori,Mitsutaka Yoshida,Yohei Takashima,Takahiro Suzuki,Yojiro Kawabe,Osamu Cynshi,Tatsuhiko Kodama,Etsuo Niki,Makoto Shimizu
摘要
Antioxidants have been considered as potential antiatherogenic agents by inhibiting oxidation of low-density lipoprotein (LDL), albeit vitamin E, a natural antioxidant, has failed to show reduction on atherosclerosis in clinical trials. We have rationally designed and synthesized a novel series of antioxidants, 4,6-di-tert-butyl-2,3-dihydro-5-benzofuranols, to overcome the clinical limitation of vitamin E. In vitro, the compounds showed a potent inhibitory effect on lipid peroxidation detected as 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin-3-one (MCLA)-dependent chemiluminescence in linoleic acid autoxidation. They also inhibited the LDL oxidation induced by Cu(2+), and the inhibition is more potent than that of vitamin E and probucol. In vivo, 4,6-di-tert-butyl-2,3-dihydro-2,2-dipentyl-5-benzofuranol (BO-653, 1f), an optimal compound, showed the highest concentration in plasma and LDL fraction in Watanabe heritable hyperlipidemic rabbits, due to its high affinity to LDL. The isolated LDL samples from the 1f-treated rabbits showed potent resistibility to LDL oxidation. Compound 1f has been taken into clinical trials.
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