Hemozoin is generally considered a waste deposit that is formed for the sole purpose of detoxification of free heme that results from the digestion of hemoglobin by parasites. However, several observations of parasite multiplication, both in vertebrate and invertebrate hosts are suggestive of a wider, but overlooked, metabolic role for this product. The presence of clinical peripheral blood samples of with high parasitemia containing only hemozoin-deficient (non-pigmented) asexual forms has been repeatedly confirmed. Such samples stand in contrast with other samples that contain mostly pigmented circulating trophozoites and gametocytes, indicating that pigment accumulation is a prominent feature of gametocytogenesis. The restricted size, i.e. below detection by light microscopy, of hemozoin in asexual merozoites and ringforms of implies its continuous turnover, supporting a role in metabolism. The prominent interaction of hemozoin with several antimalarial drugs, the involvement of proteins in hemozoin formation, and the finding of plasmodial genes coding for a heme-oxygenase-like protein argue for a wider and more active role for hemozoin in the parasite's metabolism. The observed association of hemozoin with crystalloids during ookinete development is consistent with a useful function to it during parasite multiplication in the invertebrate host. Finally, alternative mechanisms, other than hemozoin formation, provide substitute or additional routes for heme detoxification.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415077 | PMC |
Publication Analysis
Top Keywords
Similar Publications
Benzimidazole analogues active against adult Schistosoma mansoni: SAR analyses, In vivo efficacy in mice, and preliminary mechanistic studies as potential inhibitors of hemozoin formation.
Eur J Med Chem
December 2024
Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland; University of Basel, P.O. Box CH-4003, Basel, Switzerland. Electronic address:
For over three decades, praziquantel (PZQ) has been the mainstay chemotherapy for prevention and treatment of schistosomiasis. The excessive use of PZQ, coupled with the lack of advanced drug candidates in the current anti-schistosomiasis drug development pipeline, emphasizes the genuine need for new drugs. In the current work, we investigated the antischistosomal potential of a new series of compounds derived from the privileged benzimidazole scaffold, which exhibited low micromolar IC potency in the range of 1.
View Article and Find Full Text PDFTKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent Antimalarial Activity and a High Barrier to Resistance.
J Med Chem
December 2024
Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Pharmaceutical and Medicinal Chemistry, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Malaria continues to pose a significant burden on populations in endemic areas and requires innovative treatment options. Here, we report the synthesis and preclinical evaluation of the novel 3-hydroxypropanamidine (HPA) , which shows excellent antiplasmodial activity against drug-sensitive and -resistant strains. Moreover, in various human cell lines, the compound shows no cytotoxicity and excellent parasite selectivity.
View Article and Find Full Text PDFImpact on parasitemia, survival time and pro-inflammatory immune response in mice infected with treated with .
Front Pharmacol
December 2024
Postgraduate Program in Biodiversity and Biotechnology, Federal University of Pará, Belém, Brazil.
studies with have demonstrated the antiparasitic activity of , attributed to its naphthoquinones. This study reports on pro-inflammatory changes in mice infected with and correlates these changes with parasitemia and survival. The ethanol extract of (EEEp) was fractionated under reflux to obtain the dichloromethane fraction (FDMEp) and isolated compounds from , relating these to survival time and parasitemia.
View Article and Find Full Text PDFStage-specific pharmacodynamic chloroquine and pyronaridine action on artemisinin ring-stage resistant Kelch C580Y mutation correlates to hemozoin inhibition process.
Antimicrob Agents Chemother
December 2024
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
The antimalarial quinolines pyronaridine and chloroquine both inhibit hemozoin crystallization, predominately produced by intra-erythrocytic trophozoite stage parasites. Pyronaridine extends activity to ring-stage chloroquine-sensitive parasites, in contrast to chloroquine. Here, we investigated chloroquine and pyronaridine hemozoin inhibition type correlated to stage-specific activity on chloroquine-resistant ring-stage artemisinin sensitive and resistant CamWT and CamWT-C580Y parasites.
View Article and Find Full Text PDFMalaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.
Elife
December 2024
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection, parasites internalize and digest abundant host hemoglobin within the digestive vacuole. This massive catabolic process generates copious free heme, most of which is biomineralized into inert hemozoin.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!