Abstract
The synthesis of the chimeric molecules consisting of two pharmacophores, tetraoxane and 7-chloro-4-aminoquinoline, is reported. The tetraoxanes 2, 4, and 8 show relatively potent in vitro antimalarial activities, with IC90 values for the Plasmodium falciparum strain W2 of 2.26, 12.44, and 10.74 nM, respectively. In addition, two compounds, 2 and 4, cured mice in a modified Thompson test for antimalarial blood stage activity, with a minimum curative dose of 80 mg/kg, a minimum active dose of 20 mg/kg/day, and a maximum tolerated dose of >960 mg/kg.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminoquinolines / chemistry*
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Animals
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Antimalarials / chemical synthesis*
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Antimalarials / chemistry
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Antimalarials / pharmacology*
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Binding Sites
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Malaria / blood
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Malaria / drug therapy*
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Malaria / parasitology
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Maximum Tolerated Dose
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Mice
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Molecular Structure
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Parasitic Sensitivity Tests
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Plasmodium falciparum / drug effects*
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Stereoisomerism
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Structure-Activity Relationship
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Tetraoxanes / chemistry*
Substances
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Aminoquinolines
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Antimalarials
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Tetraoxanes
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7-chloro-4-aminoquinoline