Abstract
Previously reported studies identified analogues of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are nontoxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges.
MeSH terms
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Administration, Oral
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Animals
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Antimalarials / administration & dosage
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Antimalarials / chemistry*
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Antimalarials / pharmacokinetics*
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Chloroquine / pharmacology
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Cytochrome P-450 CYP2D6 / metabolism
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Cytochrome P-450 CYP2D6 Inhibitors
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Disease Models, Animal
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Drug Evaluation, Preclinical
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Drug Interactions
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Female
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HEK293 Cells
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Hep G2 Cells
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Humans
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Malaria / drug therapy*
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Mice
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Mice, Inbred ICR
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Microsomes, Liver / metabolism
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Parasitemia / drug therapy
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Plasmodium berghei / drug effects*
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Propafenone / analogs & derivatives*
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Structure-Activity Relationship
Substances
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Antimalarials
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Cytochrome P-450 CYP2D6 Inhibitors
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Propafenone
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Chloroquine
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Cytochrome P-450 CYP2D6