Water Soluble Antioxidant Dextran-Quercetin Conjugate with Potential Anticancer Properties

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-1 and H-1-C-13 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 degrees 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 degrees C and 2 m HCl is shown to be cytotoxic to neuroblastoma cells (SH-SY5Y-IC50 = 123 mu g mL(-1) and BE(2)-C-IC50 = 380 mu g mL(-1)) but shows no activity against nonmalignant MRC-5 cells at concentrations up to 400 mu g mL(-1).