Abstract
A series of polyaminoguanidines and polyaminobiguanides were synthesized and evaluated as potential antitrypanosomal agents. These analogues inhibit trypanothione reductase (TR) with IC50 values as low as 0.95 microM, but do not inhibit the closely related human enzyme glutathione reductase (GR). The most effective analogues, 7a, 7b and 8d, inhibited parasitic growth in vitro with IC50 values of 0.18, 0.09 and 0.18 microM, respectively. These agents represent a promising new class of potential antitrypanosomal agents.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alkylation
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Animals
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Antiprotozoal Agents / chemical synthesis*
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Antiprotozoal Agents / chemistry
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Antiprotozoal Agents / pharmacology*
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Glutathione Reductase / antagonists & inhibitors
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Glutathione Reductase / metabolism
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Guanidines / chemical synthesis
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Guanidines / chemistry*
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Guanidines / pharmacology*
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Humans
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Molecular Structure
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NADH, NADPH Oxidoreductases / antagonists & inhibitors
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NADH, NADPH Oxidoreductases / metabolism
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Structure-Activity Relationship
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Trypanosoma brucei brucei / drug effects*
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Trypanosoma brucei brucei / physiology
Substances
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Antiprotozoal Agents
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Guanidines
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NADH, NADPH Oxidoreductases
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trypanothione reductase
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Glutathione Reductase
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pimagedine