On the molecular mechanism of chloroquine's antimalarial action.

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Sullivan DJ Jr, Gluzman IY, Russell DG, Goldberg DE

On the molecular mechanism of chloroquine's antimalarial action.

Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11865-70.

PubMed ID

8876229 [ View in PubMed

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Abstract

Chloroquine is thought to exert its antimalarial effect by preventing the polymerization of toxic heme released during proteolysis of hemoglobin in the Plasmodium digestive vacuole. The mechanism of this blockade has not been established. We incubated cultured parasites with subinhibitory doses of [3H]chloroquine and [3H] quinidine. These [3H]quinoline compounds became associated with hemozoin as assessed by electron microscope autoradiography and subcellular fractionation. In vitro, binding of [3H]quinoline inhibitors to the hemozoin chain depended on the addition of heme substrate. These data counter previous conclusions regarding the lack of quinoline association with hemozoin, explain the exaggerated accumulation of quinolines in the plasmodium digestive vacuole, and suggest that a quinoline heme complex incorporates into the growing polymer to terminate chain extension, blocking further sequestration of toxic heme.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amodiaquine	Fe(II)-protoporphyrin IX	Small molecule	Plasmodium falciparum	Yes	Binder	Details