Abstract
We attached 2-aminoethylamino groups to allophenylnorstatine-containing plasmepsin (Plm) inhibitors and investigated SAR of the methyl or ethyl substitutions on the amino groups. Unexpectedly, compounds 22 (KNI-10743) and 25 (KNI-10742) exhibited extremely potent Plm II inhibitory activities (K(i)<0.1 nM). Moreover, among our peptidomimetic Plm inhibitors, we identified the compounds with the highest antimalarial activity using a SYBR Green I-based fluorescence assay.
2010 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 / chemistry*
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Antimalarials / pharmacology
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / metabolism
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Binding Sites
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Computer Simulation
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Ethylenediamines / chemical synthesis
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Ethylenediamines / chemistry*
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Ethylenediamines / pharmacology
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Phenylbutyrates / chemistry
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacology
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Protozoan Proteins / antagonists & inhibitors*
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Protozoan Proteins / metabolism
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Structure-Activity Relationship
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Thiazoles / chemical synthesis
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Thiazoles / chemistry*
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Thiazoles / pharmacology
Substances
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Antimalarials
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Ethylenediamines
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KNI 10742
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KNI 10743
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Phenylbutyrates
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Protease Inhibitors
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Protozoan Proteins
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Thiazoles
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3-amino-2-hydroxy-4-phenylbutanoic acid
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Aspartic Acid Endopeptidases
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plasmepsin II