Australian Centre for NanoMedicine (ACN), School of Chemical Engineering, University of New South Wales, Sydney, 2052, Australia.
Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, University of New South Wales, Sydney, 2052, Australia.
Macromol Biosci. 2018 Apr;18(4):e1700239. doi: 10.1002/mabi.201700239. Epub 2018 Feb 7.
Quercetin, a naturally occurring potent antioxidant, is limited in therapeutic use, owing to its poor water solubility and stability. Herein, a method of conjugating quercetin to an aldehyde functionalized dextran via an HCl catalyzed condensation reaction to yield a water soluble quercetin functionalized polymer is reported. The prepared conjugate is characterized by H and H- C heteronuclear single quantum correlation (HSQC) NMR, which demonstrate that conjugation occurs via both the A- and B-rings of quercetin. The degree of quercetin functionalization can be tuned by varying the reaction temperature and/or the concentration of the HCl catalyst. However, as temperatures and HCl concentrations are increased above 40 °C and 2 m, respectively, the increase in functionalization is accompanied by an increase in the oxidation of the conjugated quercetin and a decrease in polymer yield. The prepared conjugate is shown to have improved stability compared with native quercetin while maintaining substantial free-radical scavenging activity. Anticancer activity is evaluated in vitro in a neuroblastoma cell line. The dextran-aldehyde-quercetin conjugate prepared at 40 °C and 2 m HCl is shown to be cytotoxic to neuroblastoma cells (SH-SY5Y-IC = 123 µg mL and BE(2)-C-IC = 380 µg mL ) but shows no activity against nonmalignant MRC-5 cells at concentrations up to 400 µg mL .
槲皮素是一种天然存在的强效抗氧化剂，但由于其水溶性和稳定性差，其治疗用途受到限制。在此，报道了一种通过 HCl 催化缩合反应将槲皮素与醛基功能化葡聚糖偶联，从而得到水溶性槲皮素功能化聚合物的方法。通过 H 和 H- C 异核单量子相关（HSQC）NMR 对制备的缀合物进行了表征，结果表明槲皮素通过 A-和 B-环与醛基功能化葡聚糖发生偶联。通过改变反应温度和/或 HCl 催化剂的浓度，可以调节槲皮素的功能化程度。然而，当温度和 HCl 浓度分别高于 40°C 和 2 m 时，功能化程度的增加伴随着共轭槲皮素的氧化增加和聚合物产率的降低。与天然槲皮素相比，所制备的缀合物具有更好的稳定性，同时保持了相当大的自由基清除活性。在神经母细胞瘤细胞系中进行了体外抗癌活性评估。在 40°C 和 2 m HCl 下制备的葡聚糖-醛-槲皮素缀合物对神经母细胞瘤细胞（SH-SY5Y-IC = 123 µg mL 和 BE(2)-C-IC = 380 µg mL ）表现出细胞毒性，但在高达 400 µg mL 的浓度下对非恶性 MRC-5 细胞没有活性。
