Heme polymerase: Modulation by chloroquine treatment of a rodent malaria
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Cited by (70)
Recent advances in biological activities of rhodium complexes: Their applications in drug discovery research
2021, European Journal of Medicinal ChemistryCitation Excerpt :Malarial hemozoin may play a vital role as a target in disease pathogenesis and antimalarial drugs developments. Chloroquine in cell-free extracts [82] and in both Plasmodium falci-parum [83] and Plasmodium berghei [84,85] inhibits the synthesis of hemozoin. Smith et al. demonstrated that the biological activity of a series of cyclometalated Rh(III) complexes (Fig. 19) was enhanced via increased lipophilicity when endowed with an organosilane entity.
Chloroquine and hydroxychloroquine in the treatment of malaria and repurposing in treating COVID-19
2020, Pharmacology and TherapeuticsUsing a genome-scale metabolic network model to elucidate the mechanism of chloroquine action in Plasmodium falciparum
2017, International Journal for Parasitology: Drugs and Drug ResistanceCitation Excerpt :Chloroquine was the first-line malaria treatment for many decades until drug-resistant P. falciparum strains became common. The drug causes a dose-dependent decrease in hemozoin formation (Chou and Fitch, 1992; Slater and Cerami, 1992) and an associated increase in toxic free heme in the food vacuole of the parasite (Combrinck et al., 2013; Loria et al., 1999). Over the past few decades, researchers have proposed many different mechanisms for chloroquine action, including 1) DNA intercalation (Meshnick, 1990), 2) alteration of digestive food vacuole pH (Yayon et al., 1985), 3) inhibition of heme polymerase (Yayon et al., 1985), and 4) formation of a toxic chloroquine-ferriprotoporphyrin IX complex (Sugioka et al., 1987).
The antimalarial drugs chloroquine and primaquine inhibit pyridoxal kinase, an essential enzyme for vitamin B6 production
2014, FEBS LettersCitation Excerpt :However, there is still argument that other target molecules mediate the antimalarial effects since the effective concentrations of inhibitors are relatively high and direct association of chloroquine and primaquine with malaria quinone reductase and malaria aldehyde dehydrogenase and inhibition of these malaria enzymes by the quinoline derivatives have not been demonstrated. On the other hand, it has also been reported that chloroquine binds to heme and inhibits heme polymerase activity in the malaria protozoan, which is critical for heme intoxication [5]. The inhibition of heme polymerization might account for the mechanism of action of chloroquine as an antimalarial agent, although the corresponding enzyme mediating heme polymerization has not been identified.
Malarial hemozoin: From target to tool
2014, Biochimica et Biophysica Acta - General SubjectsCitation Excerpt :The accumulation of heme causes severe damage to the parasite, leading to its death [107]. Based on what little was known about the mechanism of action of CQ, several studies focused on testing its role as a possible inhibitor of hemozoin (ferriprotoporphyrin IX) crystallization [36,108,109]. They concluded that chloroquine does inhibit hemozoin formation by interfering in its assembly, be it initiated by hemozoin or by trophozoite extracts [36,109,110].
Oral delivery of curcumin bound to chitosan nanoparticles cured Plasmodium yoelii infected mice
2012, Biotechnology Advances