Endoperoxide Drug Cross-Resistance Patterns for Plasmodium falciparum Exhibiting an Artemisinin Delayed-Clearance Phenotype.
The ring-stage susceptibility assay was modified to quantify the susceptibilities of multiple strains of control and delayed-clearance phenotype (DCP) Plasmodium falciparum strains to seven endoperoxide antimalarial drugs. The susceptibility of all of the DCP lines to six of the drugs was lower than that of the controls. In contrast, DCP parasites did not show reduced susceptibility to the synthetic endoperoxide drug OZ439. These data show that it is possible to circumvent emerging artemisinin resistance with a modified endoperoxide drug.
Departments of Chemistry and of Biochemistry and Cellular and Molecular Biology, Georgetown University, Washington, DC, USA.
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Siriwardana
Departments of Chemistry and of Biochemistry and Cellular and Molecular Biology, Georgetown University, Washington, DC, USA.
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Iyengar
Departments of Chemistry and of Biochemistry and Cellular and Molecular Biology, Georgetown University, Washington, DC, USA paul.roepe@georgetown.edu.
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Roepe
D000218:Adamantane / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects*; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D008658:Inactivation, Metabolic; D007928:Lethal Dose 50; D008826:Microbial Sensitivity Tests; D010545:Peroxides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D013141:Spiro Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
D000962:Antimalarials; D037621:Artemisinins; D006573:Heterocyclic Compounds, 1-Ring; D010545:Peroxides; D013141:Spiro Compounds; C489136:arterolane; C039060:artenimol; C031327:artemisinin; D000077549:Artemether; D000218:Adamantane; C558165:artefenomel