Abstract
Phenylurenyl chalcone derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-resistant strain of Plasmodium falciparum, activity of the cysteine protease falcipain-2, in vitro globin hydrolysis, beta-hematin formation, and murine Plasmodium berghei malaria. The most active antimalarial compound was 1-[3'-N-(N'-phenylurenyl)phenyl]-3(3,4,5-trimethoxyphenyl)-2-propen-1-one 49, with an IC(50) of 1.76 microM for inhibition of P. falciparum development. Results suggest that chalcones exert their antimalarial activity via multiple mechanisms.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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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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Chalcones / chemical synthesis*
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Chalcones / chemistry
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Chalcones / pharmacology
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Cysteine Endopeptidases / chemistry
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Globins / metabolism
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Heme / chemistry
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Hemeproteins / chemical synthesis
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Hydrolysis
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Malaria / drug therapy
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Mice
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Phenylurea Compounds / chemical synthesis*
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Phenylurea Compounds / chemistry
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Phenylurea Compounds / pharmacology
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Plasmodium berghei
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Plasmodium falciparum / drug effects
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Polymers
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology
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Structure-Activity Relationship
Substances
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Antimalarials
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Chalcones
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Hemeproteins
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Phenylurea Compounds
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Polymers
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Protease Inhibitors
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hemozoin
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Heme
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Globins
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Cysteine Endopeptidases
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falcipain 2