Abstract
N6-Naphthalenemethyl-2'-methoxybenzamido-beta-NAD+, a derivative of a low micromolar first-generation inhibitor of trypanosomal glyceraldehyde phosphate dehydrogenase (GAPDH), was synthesized, taking advantage of methodology for the selective phosphitylation of nucleosides. The compound was found to be a poor alternate cosubstrate for GAPDH, but an extremely potent inhibitor. Although intended for use in crystallization trials, the analogue presents possibilities for further drug design.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Antiprotozoal Agents / chemical synthesis*
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Antiprotozoal Agents / pharmacology
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Cell Culture Techniques
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors*
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Humans
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Inhibitory Concentration 50
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Mice
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Muscle, Skeletal / cytology
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NAD / analogs & derivatives*
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NAD / chemical synthesis
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NAD / pharmacology*
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Rabbits
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Structure-Activity Relationship
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Trypanosoma / drug effects*
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Trypanosoma / enzymology
Substances
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Antiprotozoal Agents
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Enzyme Inhibitors
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NAD
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Glyceraldehyde-3-Phosphate Dehydrogenases