Synthesis and Structure-Activity Relationships of 4-Pyridones as Potential Antimalarials.
Loading...
Identifiers
Publication date
Start date of the public exhibition period
End date of the public exhibition period
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Metrics
Share
Export
Abstract
A series of diaryl ether substituted 4-pyridones have been identified as having potent antimalarial activity superior to that of chloroquine against Plasmodium falciparum in vitro and murine Plasmodium yoelii in vivo. These were derived from the anticoccidial drug clopidol through a systematic study of the effects of varying the side chain on activity. Relative to clopidol the most active compounds show >500-fold improvement in IC50 for inhibition of P. falciparum in vitro and about 100-fold improvement with respect to ED50 against P. yoelii in mice. These compounds have been shown elsewhere to act selectively by inhibition of mitochondrial electron transport at the cytochrome bc1 complex.