Abstract
Solid- and solution-phase parallel syntheses of 1,4-naphthoquinones (1,4-NQ) are described. A library of 1360 amides was constructed from the combination of 12 newly synthesised 1,4-NQ carboxylic acid and 120 amines, and was screened for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi. The most active hits from a primary screening were re-synthesised and confirmed. This approach proves that it is possible to design potent and highly specific TcTR inhibitors deriving from menadione, juglone and plumbagin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Automation
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Drug Evaluation, Preclinical / methods
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Inhibitory Concentration 50
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NADH, NADPH Oxidoreductases / antagonists & inhibitors*
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Naphthoquinones / chemical synthesis*
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Naphthoquinones / chemistry
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Naphthoquinones / pharmacology
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Quality Control
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Trypanosoma cruzi / drug effects*
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Trypanosoma cruzi / enzymology
Substances
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Antiprotozoal Agents
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Naphthoquinones
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NADH, NADPH Oxidoreductases
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trypanothione reductase
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1,4-naphthoquinone