Chloroquine as intercalator: a hypothesis revived.

The mode of action of chloroquine is still controversial. Proposed mechanisms of action include (1) DNA intercalation, (2) lysosome accumulation and (3) binding to ferriprotoporphyrin IX. Recent data suggest that intercalation into parasite DNA can occur at physiological concentrations of the drug. Furthermore, structure-activity relationship studies are most consistent with the intercalation mechanism. Regardless of which mechanism is correct, the selective toxicity of chloroquine for malaria parasites is probably due to permease-mediated uptake.