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With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenicPlasmodium berghei parasite (1052Cl1;Pb GFP-Luccon ) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H )-quinolone (PEQ), as well as two 3-phenyl-4(1H )-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activityin vitro and causal prophylactic activityin vivo . This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.

4(1H)-Quinolones with Liver Stage Activity against Plasmodium berghei