PEG-scutellarin prodrugs: synthesis, water solubility and protective effect on cerebral ischemia/reperfusion injury.
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).
Lu
Juan
J
Department of Chemistry, Tsinghua University, Beijing 100084, PR China.
Cheng
Changmei
C
Zhao
Xinge
X
Liu
Qingfei
Q
Yang
Ping
P
Wang
Yiming
Y
Luo
Guoan
G
D000818:Animals; D047310:Apigenin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005965:Glucuronates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000517:prevention & control*; D015394:Molecular Structure; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D012995:Solubility; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry*
D005965:Glucuronates; D011355:Prodrugs; D014867:Water; C484876:scutellarin; D011092:Polyethylene Glycols; D047310:Apigenin