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

Journal Title

Journal ISSN

Volume Title

Publisher

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. O

Description

Keywords

Citation

Source

Antimicrobial Agents and Chemotherapy

Type

Journal article

Book Title

Entity type

Access Statement

Open Access

License Rights

Restricted until