Abstract
Several N-(3-phenylpropyl)-substituted spermidine and spermine derivatives were prepared and found to be potent competitive inhibitors of Trypanosoma cruzi trypanothione reductase (seven compounds with Ki values < 5 microM are described). The most effective inhibitor studied was compound 12 with a Ki value of 0.151 microM. Six of the compounds described are also effective trypanocides with IC50 values < 1 microM.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive
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Combinatorial Chemistry Techniques
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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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Inhibitory Concentration 50
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Kinetics
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NADH, NADPH Oxidoreductases / antagonists & inhibitors*
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Polyamines / chemical synthesis
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Polyamines / chemistry
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Polyamines / pharmacology*
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Spermidine / analogs & derivatives
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Spermine / analogs & derivatives
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Structure-Activity Relationship
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Trypanocidal Agents / chemical synthesis*
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Trypanocidal Agents / chemistry
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Trypanocidal Agents / pharmacology
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Trypanosoma brucei brucei / enzymology
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Trypanosoma cruzi / enzymology
Substances
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Enzyme Inhibitors
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Polyamines
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Trypanocidal Agents
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Spermine
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NADH, NADPH Oxidoreductases
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trypanothione reductase
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Spermidine