Synthesis and Evaluation as a Blood-Brain Barrier-Permeable Probe of 7-N-(PROXYL-3-yl-methyl)theophylline

被引：8
|
作者：
Emoto, Miho C. [1 ]
Sasaki, Kota [2 ]
Maeda, Koya [2 ]
Fujii, Hirotada G. [1 ]
Sato, Shingo [2 ]
机构：
[1] Sapporo Med Univ, Ctr Med Educ, Sapporo, Hokkaido 0608556, Japan
[2] Yamagata Univ, Grad Sch Sci & Engn, Dept Biochem Engn, 4-3-16 Jonan, Yonezawa, Yamagata 9928510, Japan
来源：
CHEMICAL & PHARMACEUTICAL BULLETIN | 2018年 / 66卷 / 09期
基金：
日本学术振兴会;
关键词：
theophylline; pyrrolidine nitroxide; blood-brain barrier; redox status; FREE-RADICAL REACTIONS; NITROXYL-PROBES; ASCORBIC-ACID; REDUCTION; GLUTATHIONE; DISEASE; MOUSE;
D O I：
10.1248/cpb.c18-00333
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The drug-nitroxide radical hybrid-compound 7-N-((2,2,5,5-tetramethylpyrrolidine-1-yloxy(PROXYL))-3-yl-methyl)theophylline (3) was synthesized by coupling 7-N-tosyltheophylline with 3-hydroxymethyl-PROXYL, HMP). The stability of 3 relative to that of HMP was examined in the presence of the anti-oxidant, ascorbic acid (AsA). The initial reduction rate constants of 3 and HMP were 11.9 +/- 5.3 and w6.1 +/- 5.2 M-1 min(-1), respectively. In the presence of glutathione (GSH), these constants increased slightly to 22.3 +/- 6.8 and 9.1 +/- 2.4 M-1 min(-1), respectively. Two-dimensional cranial electron paramagnetic resonance imaging of mice intravenously injected with 3 via the tail vein revealed that probe 3 enters the mouse brain by passing through the blood-brain barrier (BBB).
引用
收藏
页码：887 / 891
页数：5
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