Abstract
To improve the entry of certain drugs into brain, ascorbic acid (AA) conjugates of these drugs were synthesized and their capacity to interact with SVCT2 ascorbate transporters was explored. Kinetic studies clearly indicate that all of the conjugates were able to competitively inhibit ascorbate transport in human retinal pigment epithelial cells (HRPE). In vivo studies, in a mouse model system, demonstrate that conjugate 3 is better absorbed compared to the nonconjugated parent drug.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Ascorbic Acid / chemistry*
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Ascorbic Acid / metabolism
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Biological Transport
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Cell Line
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Central Nervous System Agents / chemical synthesis*
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Central Nervous System Agents / chemistry
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Central Nervous System Agents / pharmacology
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Diclofenac / chemistry*
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Humans
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Kinetics
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Kynurenic Acid / chemistry*
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Mice
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Nipecotic Acids / chemistry*
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Organic Anion Transporters, Sodium-Dependent / metabolism
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology
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Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Seizures / drug therapy
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Sodium-Coupled Vitamin C Transporters
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Structure-Activity Relationship
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Symporters*
Substances
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Central Nervous System Agents
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Nipecotic Acids
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Organic Anion Transporters, Sodium-Dependent
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Prodrugs
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Proteins
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SLC23A2 protein, human
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Slc23a2 protein, mouse
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Sodium-Coupled Vitamin C Transporters
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Symporters
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Diclofenac
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nipecotic acid
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Kynurenic Acid
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Ascorbic Acid