A Pantetheinase-Resistant Pantothenamide with Potent, On Target, and Selective Antiplasmodial Activity
Date
2015
Authors
Macuamule, Cristiano
Tjhin, Erick
Jana, Collins E.
Barnard, Leanne
Koekemoer, Lizbe
de Villiers, Marianne
Saliba, Kevin
Strauss, Erick
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American Society for Microbiology
Abstract
Pantothenamides inhibit blood-stage Plasmodium falciparum with potencies (50% inhibitory concentration [IC50], 20 nM)
similar to that of chloroquine. They target processes dependent on pantothenate, a precursor of the essential metabolic cofactor
coenzyme A. However, their antiplasmodial activity is reduced due to degradation by serum pantetheinase. Minor modification
of the pantothenamide structure led to the identification of -methyl-N-phenethyl-pantothenamide, a pantothenamide resistant
to degradation, with excellent antiplasmodial activity (IC50, 52 6 nM), target specificity, and low toxicity.
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Antimicrobial Agents and Chemotherapy
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Journal article
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Open Access
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