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 - Villiers, Marianne de
AU - Saliba, Kevin J.
AU - Strauss, Erick
PY - 2015
Y1 - 2015
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 _-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 _-methyl-N-phenethyl-pantothenamide, a pantothenamide resistant to degradation, with excellent antiplasmodial activity (IC50, 52_6 nM), target specificity, and low toxicity.
KW - Plasmodium falciparum
KW - coenzymes
UR - http://handle.westernsydney.edu.au:8081/1959.7/uws:46224
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 -
