Abstract
The synthesis and biological evaluation of two novel series of natural-product-like hybrids based on the chalcone, thiolactone and isatin scaffolds is herein described. Results for a 36-member beta-amino alcohol triazole library showed that the thiolactone-chalcones, with IC(50)s ranging from 0.68 to 6.08 microM, were more active against W2 strain Plasmodium falciparum than the isatin-chalcones with IC(50)s of 14.9 microM or less. Also of interest is falcipain-2 inhibitory activity displayed by the latter, whereas the thiolactone-chalcones lacked enzyme inhibitory activity.
2010 Elsevier Ltd. All rights reserved.
Publication types
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Comparative Study
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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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Chalcone / chemical synthesis
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Chalcone / chemistry
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Chalcone / pharmacology*
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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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Humans
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Isatin / chemical synthesis
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Isatin / chemistry
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Isatin / pharmacology
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Lactones / chemical synthesis
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Lactones / chemistry
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Lactones / pharmacology
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Malaria, Falciparum / drug therapy
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Plasmodium falciparum / drug effects*
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Plasmodium falciparum / enzymology*
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Triazoles / chemical synthesis
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Triazoles / chemistry
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Triazoles / pharmacology*
Substances
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Antimalarials
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Cysteine Proteinase Inhibitors
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Lactones
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Triazoles
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Chalcone
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Isatin
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Cysteine Endopeptidases
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falcipain