Journal
ACS INFECTIOUS DISEASES
Volume 9, Issue 8, Pages 1647-1657Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.3c00278
Keywords
chloroquine; HDP; hemozoin; heme; Plasmodium; avrami; beta-hematin
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Malaria parasites produce toxic heme during hemoglobin digestion, which is neutralized by crystallizing into inert hemozoin. Chloroquine inhibits this detoxification process, but its exact mechanism of action is unknown. This study found that chloroquine slows down the transformation of heme into hemozoin, but does not affect the availability of the substrate or the formation of hemozoin. The presence of chloroquine increases the size of hemozoin crystals, suggesting that it delays hemozoin production by interfering with crystal nucleation or stability.
Malaria parasites generate toxic heme during hemoglobin digestion, which is neutralized by crystallizing into inert hemozoin (beta-hematin). Chloroquine blocks this detoxification process, resulting in heme-mediated toxicity in malaria parasites. However, the exact mechanism of chloroquine's action remains unknown. This study investigates the impact of chloroquine on the transformation of heme into beta-hematin. The results show that chloroquine does not completely halt the transformation process but rather slows it down. Additionally, chloroquine complexation with free heme does not affect substrate availability or inhibit beta-hematin formation. Scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) studies indicate that the size of beta-hematin crystal particles and crystallites increases in the presence of chloroquine, suggesting that chloroquine does not impede crystal growth. These findings suggest that chloroquine delays hemozoin production by perturbing the nucleation events of crystals and/or the stability of crystal nuclei. Thus, contrary to prevailing beliefs, this study provides a new perspective on the working mechanism of chloroquine.
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