| Abstract
| - Third world nations require immediate access to inexpensive therapeutics to counter the high mortalityinflicted by malaria. Here, we report a new class of antimalarial protein farnesyltransferase (PFT) inhibitors,designed with specific emphasis on simple molecular architecture, to facilitate easy access to therapiesbased on this recently validated antimalarial target. This novel series of compounds represents the firstPlasmodiumfalciparum selective PFT inhibitors reported (up to 145-fold selectivity), with lead inhibitorsdisplaying excellent in vitro activity (IC50< 1 nM) and toxicity to cultured parasites at low concentrations(ED50< 100 nM). Initial studies of absorption, metabolism, and oral bioavailability are reported.
|
