Design, synthesis and preliminary biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen
2013; Elsevier BV; Volume: 24; Issue: 2 Linguagem: Inglês
10.1016/j.cclet.2013.01.022
ISSN1878-5964
AutoresXueying Wu, Xiaocen Li, Jie Mi, Jing You, Li Hai,
Tópico(s)Vitamin D Research Studies
Resumol-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 C6O conjugation has been investigated as a tool to enhance brain drug delivery, C5O conjugation and C5O & C6O conjugation as brain targeting tools have not been reported. In this letter, ibuprofen was linked directly to C5O, C6O and C5O & C6O positions of l-ascorbic 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 C5O & C6O positions were both modified, had good targeting ability for brain which will provide an important evidence for our further study on C5O- & C6O- di-derivatives of l-ascorbic acid.
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