TY - JOUR
T1 - A pantetheinase-resistant pantothenamide with potent, on-target, and selective antiplasmodial activity
AU - Macuamule, Cristiano J.
AU - Tjhin, Erick T.
AU - Jana, Collins E.
AU - Barnard, Leanne
AU - Koekemoer, Lizbé
AU - De Villiers, Marianne
AU - Saliba, Kevin J.
AU - Strauss, Erick
N1 - Publisher Copyright:
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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 α-methyl-N-phenethyl-pantothenamide, a pantothenamide resistant to degradation, with excellent antiplasmodial activity (IC50, 52 ± 6 nM), target specificity, and low toxicity.
AB - 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 α-methyl-N-phenethyl-pantothenamide, a pantothenamide resistant to degradation, with excellent antiplasmodial activity (IC50, 52 ± 6 nM), target specificity, and low toxicity.
UR - http://www.scopus.com/inward/record.url?scp=84929629237&partnerID=8YFLogxK
U2 - 10.1128/AAC.04970-14
DO - 10.1128/AAC.04970-14
M3 - Article
SN - 0066-4804
VL - 59
SP - 3666
EP - 3668
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 6
ER -