ArticleScientific reports2016
Plasmodium falciparum Choline Kinase Inhibition Leads to a Major Decrease in Phosphatidylethanolamine Causing Parasite Death.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments.Molecules (Basel, Switzerland) · 2020Pooled it
- Lipidomic Profiling of Colonic Contents in Mice with AcuteMicroorganisms · 2026Article
- Identification and Characterization of Entamoeba histolytica Choline Kinase.Acta parasitologica · 2024Article
- Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights.Journal of fungi (Basel, Switzerland) · 2024Review
- Article
- Article
- Tandem mass tag (TMT)-based proteomic analysis of Cryptosporidium andersoni oocysts before and after excystation.Parasites & vectors · 2021Article
- New Compounds with Bioisosteric Replacement of Classic Choline Kinase Inhibitors Show Potent Antiplasmodial Activity.Pharmaceutics · 2021Article
- Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases.Pharmaceutics · 2021Review
- Linking nutrient sensing and gene expression in Plasmodium falciparum blood-stage parasites.Molecular microbiology · 2021Review
- Review
- Stressed Out AboutFrontiers in cellular and infection microbiology · 2021Review
- System-wide biochemical analysis reveals ozonide antimalarials initially act by disrupting Plasmodium falciparum haemoglobin digestion.PLoS pathogens · 2020Article
- ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents.BioMed research international · 2020Review
- Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood.The Journal of biological chemistry · 2018Review
- Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis.GigaScience · 2018Article
- PS, It's Complicated: The Roles of Phosphatidylserine and Phosphatidylethanolamine in the Pathogenesis of Candida albicans and Other Microbial Pathogens.Journal of fungi (Basel, Switzerland) · 2018Review
- ProbingWellcome open research · 2018Article
- Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Malaria is a life-threatening disease caused by different species of the protozoan parasite Plasmodium, with P. falciparum being the deadliest. Increasing parasitic resistance to existing antimalarials makes the necessity of novel avenues to treat this disease an urgent priority. The enzymes responsible for the synthesis of phosphatidylcholine and phosphatidylethanolamine are attractive drug targets to treat malaria as their selective inhibition leads to an arrest of the parasite's growth and cures malaria in a mouse model. We present here a detailed study that reveals a mode of action for two P. falciparum choline kinase inhibitors both in vitro and in vivo. The compounds present distinct binding modes to the choline/ethanolamine-binding site of P. falciparum choline kinase, reflecting different types of inhibition. Strikingly, these compounds primarily inhibit the ethanolamine kinase activity of the P. falciparum choline kinase, leading to a severe decrease in the phosphatidylethanolamine levels within P. falciparum, which explains the resulting growth phenotype and the parasites death. These studies provide an understanding of the mode of action, and act as a springboard for continued antimalarial development efforts selectively targeting P. falciparum choline kinase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.