Figure 2.

Possible mechanism (s) of action of chloroquine during blood stage malaria infection. After invasion of erythrocytes, Plasmodium parasites form their own DV, a lysosome-like acidic compartment important for parasite metabolism and survival. In acidic DVs, the host-hemoglobin is degraded by parasite proteases for the vital needs, such as amino acids and the free-heme (Fe²⁺–protophorphyrin IX) is detoxified by converting it into insoluble crystals hemozoin (Fe³⁺–protophorphyrin IX). A weak base chloroquine accumulates in DVs, increases DV pH and binds heme and crystal surfaces, thereby blocks every steps of hemozoin formation which eventually leads heme toxicity and parasite death. In the absence of hemoglobin degrading proteases hemoglobin remains undigested and free heme is significantly diminished and the effect of chloroquine on parasites does not occur. Ineffective presence of chloroquine, on the other hand, may create the chloroquine-resistant parasites via a mutation in P. falciparum chloroquine resistance transporter (PfCRT) and possibly other genes.