Abstract
A series of four prodrugs directed against Trypanosoma brucei aldolase bearing various transient enzyme-labile phosphate protecting groups was developed. Herein, we describe the synthesis and evaluation of cell permeation of these prodrugs. The oxymethyl derivative was the most efficient prodrug with a good recovering of the free drug (IC(50)=20 microM) and without any measurable cytotoxicity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde-Lyases / antagonists & inhibitors*
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Animals
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Cell Membrane Permeability / drug effects*
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Drug Delivery Systems
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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In Vitro Techniques
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Organophosphates / chemical synthesis
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Organophosphates / chemistry
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Organophosphates / pharmacology*
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Parasitic Sensitivity Tests
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Prodrugs / chemical synthesis
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Prodrugs / chemistry
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Prodrugs / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
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Trypanosoma brucei brucei / cytology
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Trypanosoma brucei brucei / drug effects
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Trypanosoma brucei brucei / enzymology*
Substances
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Enzyme Inhibitors
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Organophosphates
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Prodrugs
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Aldehyde-Lyases