Citation: Xue-Ying Wu, Xiao-Cen Li, Jie Mi, Jing You, Li Hai. Design, synthesis and preliminary biological evaluation of brain targeting L-ascorbic acid prodrugs of ibuprofen[J]. Chinese Chemical Letters, ;2013, 24(2): 117-119. shu

Design, synthesis and preliminary biological evaluation of brain targeting L-ascorbic acid prodrugs of ibuprofen

Xue-Ying Wu ^a ,
Xiao-Cen Li ^b ,
Jie Mi ^b ,
Jing You ^b ,
Li Hai ^b,,

1.
a College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China;
2.
b Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China

Corresponding author: Li Hai,
Received Date: 4 November 2012
Available Online: 31 December 2012
Fund Project: This work was supported by the Ph.D. Programs Foundation of Ministry of Education of China (No. 20110181130011) (No. 20110181130011)the National Natural Science Foundation of China (No. 81072532). (No. 81072532)

L-Ascorbic acid (AA, vitamin C) exhibits a high concentration in the brain. The transportation of AA in brain is mainly mediated by the glucose transporter 1 (GLUT₁) and the Na⁺-dependent vitamin C transporter SVCT₂. While L-ascorbic acid C6-O conjugation has been investigated as a tool to enhance brain drug delivery, C5-O conjugation and C5-O & C6-O conjugation as brain targeting tools have not been reported. In this letter, ibuprofen was linked directly to C5-O, C6-O and C5-O & C6-O positions of Lascorbic acid with eater bonds, providing prodrug 1, 2 and 3, respectively, to improve their targeting abilities in the brain. Prodrug 1, 2 and 3 were synthesized in facile ways with good yields. And the preliminary evaluation in vivo illustrated that prodrug 2 had a better targeting ability than prodrug 1. Moreover, prodrug 3, whose C5-O & C6-O positions were both modified, had good targeting ability for brain which will provide an important evidence for our further study on C5-O-& C6-O-di-derivatives of L-ascorbic acid.
- Vitamin C,
- Brain target,
- Prodrug,
- GLUT₁ transporter,
- SVCT₂ transporter,
- Ibuprofen
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