Abstract
Novel quinazoline-type compounds were designed as inhibitors of the parasite specific enzyme trypanothione reductase (TR), and their biological activities were evaluated. Some of our compounds inhibited TR, showed selectivity for TR over human glutathione reductase, and inhibited parasite growth in vitro. We propose that the quinazoline framework is a privileged structure that can be purposely modified to design novel TR inhibitors. Furthermore, the use of privileged motifs might emerge as an innovative approach to antiparasitic lead candidates.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiparasitic Agents / chemical synthesis
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Antiparasitic Agents / chemistry*
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Antiparasitic Agents / toxicity
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Cell Line
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Computer Simulation
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / toxicity
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Glutathione Reductase / antagonists & inhibitors
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Glutathione Reductase / metabolism
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Humans
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NADH, NADPH Oxidoreductases / antagonists & inhibitors*
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NADH, NADPH Oxidoreductases / metabolism
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Quinazolines / chemical synthesis
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Quinazolines / chemistry*
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Quinazolines / toxicity
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Rats
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Structure-Activity Relationship
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Trypanosoma cruzi / drug effects
Substances
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Antiparasitic Agents
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Enzyme Inhibitors
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Quinazolines
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NADH, NADPH Oxidoreductases
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trypanothione reductase
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Glutathione Reductase