PEG-scutellarin prodrugs: Synthesis, water solubility and protective effect on cerebral ischemia/reperfusion injury

被引：76

作者：

Lu, Juan ^{[1
]}

Cheng, Changmei ^{[1
]}

Zhao, Xinge ^{[2
]}

Liu, Qingfei ^{[3
]}

Yang, Ping ^{[1
]}

Wang, Yiming ^{[1
]}

Luo, Guoan ^{[1
]}

机构：

[1] Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China

[2] Jiangsu Simcere Pharmaceut Res Inst, Nanjing 210042, Peoples R China

[3] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 05期

关键词：

Scutellarin; PEG-scutellarin prodrugs; Cerebral ischemia/reperfusion injury; Middle cerebral artery occlusion model; Half-life; DELIVERY;

D O I：

10.1016/j.ejmech.2010.01.006

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

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). (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：1731 / 1738

页数：8

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