Abstract
The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an attractive antimalarial target. Here, we discovered that the natural compound NP1024 is a nonpeptidic inhibitor of FP-2 with an IC50 value of 0.44 μmol L-1. The most exciting finding is that both in vitro and in vivo, NP1024 directly targets FP-2 in malaria parasite-infected erythrocytes as a natural fluorescent probe, thereby paving the way for an integration of malaria diagnosis and treatment.
Keywords:
acylated flavonol monoglycoside; antimalarial agent; falcipain-2; fluorescent probe; malaria diagnosis.
MeSH terms
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Amino Acid Sequence
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Animals
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Antimalarials / chemistry*
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Antimalarials / metabolism
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Binding Sites
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Biological Products / chemistry*
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Biological Products / metabolism
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Cysteine Endopeptidases / metabolism*
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Cysteine Proteinase Inhibitors / chemistry*
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Cysteine Proteinase Inhibitors / metabolism
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Disease Models, Animal
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Erythrocytes / metabolism
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Fluorescent Dyes / chemistry*
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Fluorescent Dyes / metabolism
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Humans
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Inhibitory Concentration 50
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Kinetics
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Malaria / diagnostic imaging*
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Malaria / drug therapy*
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Male
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Mice
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Models, Molecular
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Molecular Targeted Therapy
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Optical Imaging
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Plasmodium falciparum / metabolism
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Protein Binding
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Protein Conformation
Substances
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Antimalarials
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Biological Products
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Cysteine Proteinase Inhibitors
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Fluorescent Dyes
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Cysteine Endopeptidases
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falcipain 2