Department of Chemistry, Tsinghua University, Beijing 100084, PR China.
Eur J Med Chem. 2010 May;45(5):1731-8. doi: 10.1016/j.ejmech.2010.01.006. Epub 2010 Jan 14.
Fifteen PEG-scutellarin prodrugs were synthesized by modifying carboxyl and phenolic hydroxyl groups of scutellarin with mPEG of different molecular weight (400-3000). The water solubility of prodrugs increased remarkably and reached the maximum value of 783.88 mg/mL (scutellarin, 0.02 mg/mL). The anti-infarct effects of four PEG prodrugs with high water solubility were evaluated by Cerebral Ischemia/Reperfusion in the Middle Cerebral Artery Occlusion (MCAO) model. The results showed that the prodrug 7e could significantly reduce the infarct area from 27.2% to 12.2% (33.3% for the control) and decrease the neurological deficit score from 2.77 to 1.32 (2.85 for the control). The half-life (18.62 min) of the prodrug 7e was significantly longer than that of scutellarin (3.03 min).
合成了 15 种 PEG-野黄芩苷前药，通过修饰野黄芩苷的羧基和酚羟基与不同分子量的 mPEG（400-3000）。前药的水溶性显著提高，达到 783.88mg/mL（野黄芩苷为 0.02mg/mL）的最大值。通过大脑中动脉闭塞（MCAO）模型评估四种具有高水溶性的 PEG 前药的抗梗死作用。结果表明，前药 7e 可使梗死面积从 27.2%显著降低至 12.2%（对照组为 33.3%），并使神经功能缺损评分从 2.77 降低至 1.32（对照组为 2.85）。前药 7e 的半衰期（18.62 分钟）明显长于野黄芩苷（3.03 分钟）。
