In vitro erythrocytic uptake studies of artemisinin and selected derivatives using LC–MS and 2D-QSAR analysis of uptake in parasitized erythrocytes

The purpose of the present investigation was to characterize the partitioning of artemisinin and its derivatives into both non-parasitized as well as Plasmodium falciparum parasitized red blood cells (RBCs). Artemisinin and selected derivatives at concentrations of 3.55 μM were incubated in RBCs with a hematocrit of 33% for 2 h at 37 °C, extracted from RBCs by solid phase extraction, and analyzed using liquid chromatography–mass spectrometry in positive electro-spray ionization mode with methanol as mobile phase. The uptake percent of artemisinin and selected derivatives into the non-parasitized RBCs ranged between 35% and 45%, while that into parasitized RBCs was between 51% and 72%. The results suggested that artemisinin and selected derivatives were preferentially distributed in parasitized RBCs. A Multiple Linear Regression model was built to gain insight about the essential structural properties required for the uptake of this class of compounds in parasitized RBCs and will provide instruction for designing of new derivatives of this class of compounds with improved uptake.

Uptake studies of artemisinin and selected derivatives into normal and parasitized red blood cells (RBCs) and Multiple Regression Model for percent uptake of artemisinin and its derivates into the parasitized RBCs.Figure optionsDownload as PowerPoint slide