Reduced digestive vacuolar accumulation of chloroquine is not linked to resistance to chloroquine toxicity.
Chloroquine (CQ) accumulation studies in live malaria parasites are typically conducted at low nanomolar CQ concentrations, and definition of CQ resistance (CQR) has been via growth inhibition assays versus low-dose CQ (i.e., via IC(50) ratios). These data have led to the nearly universally accepted idea that reduced parasite CQ accumulation is the underlying basis of CQR. Surprisingly, when quantifying CQR via cytocidal CQ activity and examining CQ accumulation at medically relevant LD(50) doses, we find reduced CQ accumulation is not the underlying cause of CQR.
Cabrera
Mynthia
M
Department of Chemistry, Georgetown University, 37th and O Streets NW, Washington, DC 20057, USA.
Paguio
Michelle F
MF
Xie
Changan
C
Roepe
Paul D
PD
D000962:Antimalarials / Q000378:metabolism* / Q000633:toxicity*; D002738:Chloroquine / Q000378:metabolism* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology*; D020128:Inhibitory Concentration 50; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D000962:Antimalarials; D002738:Chloroquine