Abstract
Azadipeptide nitriles-novel cysteine protease inhibitors-display structure-dependent antimalarial activity against both chloroquine-sensitive and chloroquine-resistant lines of cultured Plasmodium falciparum malaria parasites. Inhibition of parasite's hemoglobin-degrading cysteine proteases was also investigated, revealing the azadipeptide nitriles as potent inhibitors of falcipain-2 and -3. A correlation between the cysteine protease-inhibiting activity and the antimalarial potential of the compounds was observed. These first generation azadipeptide nitriles represent a promising new class of compounds for antimalarial drug development.
Copyright 2009 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimalarials / chemical synthesis
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Antimalarials / chemistry*
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Antimalarials / pharmacology
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Aza Compounds / chemistry*
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Cysteine Endopeptidases / chemistry*
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Cysteine Endopeptidases / metabolism
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Cysteine Proteinase Inhibitors / chemical synthesis
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Cysteine Proteinase Inhibitors / chemistry*
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Cysteine Proteinase Inhibitors / pharmacology
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Dipeptides / chemistry*
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Nitriles / chemical synthesis
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Nitriles / chemistry*
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Nitriles / pharmacology
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Plasmodium falciparum / drug effects
Substances
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Antimalarials
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Aza Compounds
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Cysteine Proteinase Inhibitors
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Dipeptides
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Nitriles
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Cysteine Endopeptidases
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falcipain 2
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falcipain 3