Abstract
A new series of side-chain modified 4-aminoquinolines have been synthesized and found active against P. falciparum in vitro and P. yoelli in vivo. Compounds 6, 11, 12, and 19 exhibited superior in vitro activity compared to chloroquine. Selected compounds 6, 12, and 19 exhibited significant suppression in the in vivo assay. These analogs form a complex with hematin and inhibit the beta-hematin formation, suggesting that this class of compounds act on a heme polymerization target.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminoquinolines / chemical synthesis*
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Aminoquinolines / chemistry
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Aminoquinolines / pharmacology
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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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Hemeproteins / antagonists & inhibitors
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Hemeproteins / biosynthesis
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Mice
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Parasitic Sensitivity Tests
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Plasmodium falciparum / drug effects
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Plasmodium yoelii / drug effects
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Structure-Activity Relationship
Substances
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Aminoquinolines
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Antimalarials
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Hemeproteins
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hemozoin