In vitro and in vivo efficacy and in vitro metabolism of 1-phenyl-3-aryl-2-propen-1-ones against Plasmodium falciparum

Investigation of a series of 1-phenyl-3-aryl-2-propen-1-ones resulted in the identification of nine inhibitors with submicromolar efficacy against at least one Plasmodium falciparum strain in vitro. These inhibitors were inactive when given orally in a Plasmodium berghei infected mouse model. Significant compound degradation occurred upon their exposure to a liver microsome preparation, suggesting metabolic instability may be responsible for the lack of activity in vivo.

Graphical abstractNine in vitro submicromolar inhibitors of Plasmodium falciparum were identified, including compound 22. They were inactive when administered orally to Plasmodium berghei infected mice, possibly due to metabolic instability.Figure optionsDownload full-size imageDownload as PowerPoint slide