"Artemisone uptake in Plasmodium falciparum-infected erythrocytes."

Antimicrob Agents Chemother. 2010 Dec 6. [Epub ahead of print]

Artemisone uptake in Plasmodium falciparum-infected erythrocytes.
Pooley S, Fatih F, Krishna S, Gerisch M, Haynes RK, Wong HN, Staines HM.

Centre for Infection, Division of Cellular and Molecular Medicine, St. George's, University of London, Cranmer Terrace, London SW17 0RE, Great Britain; Bayer Schering Pharma AG, DMPK, 42096 Wuppertal, Germany; and Department of Chemistry, Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (PR China).

Abstract

Artemisone is one of the most promising artemisinin derivatives in clinical trials. Previous studies with radiolabelled artemisinin and dihydroartemisinin have measured uptake in P. falciparum-infected erythrocytes. Uptake is much greater in infected compared with uninfected erythrocytes but the relative contributions of transport, binding and metabolism to this process still await definition. In this study, we characterised mechanisms by which [(14)C] artemisone in taken up into uninfected and P. falciparum-infected human erythrocytes in vitro. Radiolabelled artemisone rapidly enters uninfected erythrocytes without much exceeding extracellular concentrations. Unlabelled artemisone does not compete in this process. Radiolabelled artemisone is concentrated greatly by a time- and temperature-dependent mechanism in infected erythrocytes. This uptake is abrogated by unlabelled artemisone. In addition, the uptake of artemisone into three subcellular fractions, and its distribution into these fractions, is examined as a function of parasite maturation. These data are relevant to understanding the mechanisms of action of this important class of drug.
PMID: 21135191 [PubMed - as supplied by publisher]