title: Effect of artemisinin (qinghaosu) and chloroquine on drug-sensitive and drug-resistant strains of Plasmodium falciparum malaria: use of [2,8-3H]adenosine as an alternative to [G-3H]hypoxanthine in the assessment of in vitro antimalarial activity.
abstract: Using [G-3H]hypoxanthine uptake as a radioactive indicator for the growth of malarial parasites, we measured the antimalarial activity of artemisinin (Qinghaosu, QHS) against FCMSU1/Sudan strain (chloroquine-sensitive strain) and FCB K+ strain (chloroquine-resistant strain) of Plasmodium falciparum in continuous culture in vitro. The 50% inhibitory concentrations (IC50) for QHS against FCMSU1/Sudan strain and FCB K+ strain were 2.8 X 10(-8) and 3.0 X 10(-8) M, respectively. On the contrary, the response of the two strains to chloroquine was quite different. The IC50 for chloroquine against FCMSU1/Sudan strain was 5.6 ng/ml, whereas that for the FCB K+ strain was 65.6 ng/ml. Therefore, QHS did not appear to exhibit any cross-resistance with chloroquine. If [2,8-3H]adenosine was used as a radioactive precursor instead of [G-3H]hypoxanthine for the determination of antimalarial activity, virtually identical results were obtained. Therefore, [2,8-3H]adenosine can be used as an alternative to [G-3H]hypoxanthine for the assessment of antimalarial action.
authors.affiliation: Department of Pharmacology and Toxicology, West Virginia University Medical Center, Morgantown 26506.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Ye
authors.forename: K
authors.initials: K
authors.lastname: Van Dyke
authors.forename: M
authors.initials: M
authors.lastname: Wimmer
mesh_terms: D000241:Adenosine / Q000493:pharmacokinetics*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000493:pharmacokinetics*; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D007042:Hypoxanthines; D012717:Sesquiterpenes; D019271:Hypoxanthine; D002738:Chloroquine; C031327:artemisinin; D000241:Adenosine