Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859, USA.
Free Radic Biol Med. 2011 Apr 15;50(8):918-25. doi: 10.1016/j.freeradbiomed.2010.10.699. Epub 2010 Oct 23.
It is well known that antioxidants have protective effects against oxidative stress. Unfortunately, in the presence of transition metals, antioxidants, including polyphenols with potent antioxidant activities, may also exhibit pro-oxidant effects, which may irreversibly damage DNA. Therefore, antioxidants with strong free radical-scavenging abilities and devoid of pro-oxidant effects would be of immense biological importance. We report two antioxidant dendrimers with a surface rich in multiple phenolic hydroxyl groups, benzylic hydrogens, and electron-donating ring substituents that contribute to their potent free radical-quenching properties. To minimize their pro-oxidant effects, the dendrimers were designed with a metal-chelating tris(2-aminoethyl)amine (TREN) core. The dendritic antioxidants were prepared by attachment of six syringaldehyde or vanillin molecules to TREN by reductive amination. They exhibited potent radical-scavenging properties: 5 times stronger than quercetin and 15 times more potent than Trolox according to the 1,1-diphenyl-2-picrylhydrazyl assay. The antioxidant dendrimers also protected low-density lipoprotein, lysozyme, and DNA against 2,2'-azobis(2-amidinopropane) dihydrochloride-induced free radical damage. More importantly, unlike quercetin and Trolox, the two TREN antioxidant dendrimers did not damage DNA via their pro-oxidant effects when incubated with physiological amounts of copper ions. The dendrimers also showed no cytotoxicity toward Chinese hamster ovary cells.
众所周知，抗氧化剂对氧化应激具有保护作用。不幸的是，在过渡金属存在的情况下，包括具有强大抗氧化活性的多酚在内的抗氧化剂也可能表现出促氧化剂的作用，这可能会不可逆地破坏 DNA。因此，具有强大自由基清除能力且没有促氧化剂作用的抗氧化剂将具有巨大的生物学意义。我们报告了两种具有丰富的多个酚羟基、苄基氢和供电子环取代基的表面的抗氧化树突，这有助于它们具有强大的自由基猝灭特性。为了最小化其促氧化剂作用，设计了具有金属螯合三（2-氨基乙基）胺（TREN）核的树突状抗氧化剂。通过还原胺化将六个水杨醛或香草醛分子连接到 TREN 上来制备树突状抗氧化剂。根据 1,1-二苯基-2-苦基肼测定法，它们表现出强大的自由基清除特性：比槲皮素强 5 倍，比 Trolox 强 15 倍。抗氧化树突还可以保护低密度脂蛋白、溶菌酶和 DNA 免受 2,2'-偶氮双（2-脒基丙烷）二盐酸盐诱导的自由基损伤。更重要的是，与槲皮素和 Trolox 不同，当与生理量的铜离子一起孵育时，两种 TREN 抗氧化树突不会通过其促氧化剂作用破坏 DNA。树突还对中国仓鼠卵巢细胞没有细胞毒性。
