Abstract
Cations of hydroxy-substituted 1,4-naphthoquinones were
synthesized
and evaluated as antiplasmodial agents against
Plasmodium
falciparum
. The atovaquone analogues were found to be inactive
as antagonists of parasite growth, which was attributed to ionization
of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent,
the antiplasmodial activity was restored in the sub-100 nM range.
Optimal inhibitors were found to possess IC
50
values of
17.4–49.5 nM against heteroresistant
P. falciparum
W2.