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 3.55microM were incubated in RBCs with a hematocrit of 33% for 2h at 37 degrees 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.
Shah
Falgun
F
Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Zhang
Shuang-Qing
SQ
Kandhari
Shilpa Prakash
SP
Mukherjee
Prasenjit
P
Chittiboyina
Amar
A
Avery
Mitchell A
MA
Avery
Bonnie A
BA
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D016014:Linear Models; D016778:Malaria, Falciparum / Q000188:drug therapy; D013058:Mass Spectrometry; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D021281:Quantitative Structure-Activity Relationship
D000890:Anti-Infective Agents; D037621:Artemisinins; C031327:artemisinin