Department of Chemistry, Central Michigan University, Dow 343, Mount Pleasant, MI 48859, USA.
Bioorg Med Chem Lett. 2009 Nov 15;19(22):6326-30. doi: 10.1016/j.bmcl.2009.09.088. Epub 2009 Sep 25.
Three dendritic polyphenols (generation 1) were synthesized: a syringaldehyde-based dendrimer (1), a vanillin-based dendrimer (2), and an iodinated vanillin-based dendrimer (3). They all showed strong antioxidant activity according to the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical assay. The syringaldehyde dendrimer was twice and 10 times stronger than quercetin and Trolox, respectively. The vanillin-based dendrimer and its more hydrophobic iodinated derivative were also more potent antioxidants than quercetin and Trolox. The DPPH order of potency was 1>2, 3>quercetin>Trolox. All three dendrimers also protected human LDL from free radical attack in a dose-dependent manner. Their order of free radical scavenging was 1>3>2>quercetin>Trolox. The increased hydrophobic nature of the iodinated derivative may have contributed to its better LDL protection than 2. Protection of linoleic acid oxidation was studied by the beta-carotene-linoleate assay. Dendrimer 1 was clearly superior to the other antioxidants in protecting the fatty acid. In case of DNA protection against free radical damage, the order of activity was 1>quercetin>2>3, Trolox. Pro-oxidant effect on copper-induced DNA oxidation showed the following order: quercetin, Trolox>1>2>3. Results of the study show that dendritic antioxidants, even at the generation 1 level, provide promising antioxidant properties for their potential use as drug candidates for diseases associated with oxidative stress.
三种树枝状多酚（第一代）被合成：一种基于丁香醛的树突（1），一种基于香草醛的树突（2）和一种碘化香草醛的树突（3）。根据 1,1-二苯基-2-苦基肼（DPPH）自由基测定法，它们都显示出很强的抗氧化活性。丁香醛树突比槲皮素和 Trolox 分别强两倍和十倍。基于香草醛的树突及其更疏水的碘化衍生物也比槲皮素和 Trolox 具有更强的抗氧化能力。DPPH 效力顺序为 1>2，3>槲皮素>Trolox。三种树突都以剂量依赖的方式保护人 LDL 免受自由基攻击。它们的自由基清除顺序为 1>3>2>槲皮素>Trolox。碘化衍生物增加的疏水性可能有助于其比 2 更好地保护 LDL。通过β-胡萝卜素-亚油酸测定法研究了对亚油酸氧化的保护作用。树突 1 在保护脂肪酸方面明显优于其他抗氧化剂。在自由基对 DNA 损伤的保护方面，活性顺序为 1>槲皮素>2>3，Trolox。铜诱导的 DNA 氧化的促氧化剂效应表现出以下顺序：槲皮素，Trolox>1>2>3。研究结果表明，树枝状抗氧化剂，即使在第一代水平，也为其作为与氧化应激相关疾病的候选药物提供了有前途的抗氧化特性。
