ArticleAntimicrobial agents and chemotherapy2007
Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide: a possible antimalarial mechanism.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments.Molecules (Basel, Switzerland) · 2020Pooled it
- Identification and Characterization of Entamoeba histolytica Choline Kinase.Acta parasitologica · 2024Article
- Malaria therapeutics: are we close enough?Parasites & vectors · 2023Review
- Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases.Pharmaceutics · 2021Review
- ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents.BioMed research international · 2020Review
- Reviewing the Effects of Miltefosine and Suggesting It for the Treatment of Coronavirus Disease (COVID-19).Infectious diseases · 2020Review
- In Silico Investigation of First-Pass Effect on Selected Small Molecule Excipients and Structural Dynamics of P-glycoprotein.Bioinformatics and biology insights · 2020Article
- Article
- Computational Identification of Metabolic Pathways ofInternational journal of genomics · 2019Article
- Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood.The Journal of biological chemistry · 2018Review
- Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting.PLoS computational biology · 2018Article
- Human Choline Kinase-α Promotes Hepatitis C Virus RNA Replication through Modulation of Membranous Viral Replication Complex Formation.Journal of virology · 2016Article
- Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones.Antimicrobial agents and chemotherapy · 2016Article
- Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target.Journal of the National Cancer Institute · 2016Article
- Antiplasmodial activity and mechanism of action of RSM-932A, a promising synergistic inhibitor of Plasmodium falciparum choline kinase.Antimicrobial agents and chemotherapy · 2013Article
- Equal opportunity for low-degree network nodes: a PageRank-based method for protein target identification in metabolic graphs.PloS one · 2013Article
- Identification and molecular characterization of an Alba-family protein from human malaria parasite Plasmodium falciparum.Nucleic acids research · 2012Article
- The metabolic advantage of tumor cells.Molecular cancer · 2011Review
- Identification of small molecule lead compounds for visceral leishmaniasis using a novel ex vivo splenic explant model system.PLoS neglected tropical diseases · 2011Article
- Identification of inhibitors for putative malaria drug targets among novel antimalarial compounds.Molecular and biochemical parasitology · 2011Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Choline kinase is the first enzyme in the Kennedy pathway (CDP-choline pathway) for the biosynthesis of the most essential phospholipid, phosphatidylcholine, in Plasmodium falciparum. In addition, choline kinase also plays a pivotal role in trapping essential polar head group choline inside the malaria parasite. Recently, Plasmodium falciparum choline kinase (PfCK) has been cloned, overexpressed, and purified. However, the function of this enzyme in parasite growth and survival has not been evaluated owing to the lack of a suitable inhibitor. Purified recombinant PfCK enabled us to identify an inhibitor of PfCK, hexadecyltrimethylammonium bromide (HDTAB), which has a very close structural resemblance to hexadecylphosphocholine (miltefosin), the well-known antiproliferative and antileishmanial drug. HDTAB inhibited PfCK in a dose-dependent manner and offered very potent antimalarial activity in vitro against Plasmodium falciparum. Moreover, HDTAB exhibited profound antimalarial activity in vivo against the rodent malaria parasite Plasmodium yoelii (N-67 strain). Interestingly, parasites at the trophozoite and schizont stages were found to be particularly sensitive to HDTAB. The stage-specific antimalarial effect of HDTAB correlated well with the expression pattern of PfCK in P. falciparum, which was observed by reverse transcription-PCR and immunofluorescence microscopy. Furthermore, the antimalarial activity of HDTAB paralleled the decrease in phosphatidylcholine content, which was found to correlate with the decreased phosphocholine generation. These results suggest that inhibition of choline kinase by HDTAB leads to decreased phosphocholine, which in turn causes a decrease in phosphatidylcholine biosynthesis, resulting in death of the parasite.
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